PNAS: Receptor Usage & Cell Entry Of Bat Coronaviruses

More than one way to jump species

 

# 8949

 

In 2011 Hollywood director Stephen Soderbergh brought his pandemic thriller `Contagion’ to the big screen, with a fictionalized  MEV-1 bat virus as the viral villain (see Why You Should Catch `Contagion’). The following summer we became aware of a new, often deadly, respiratory virus in the Middle East – apparently also with bat origins – called MERS-CoV.

 

While one might simply assume Hollywood got `lucky’ and guessed right, the truth is the fictional MEV-1 used in the film was envisioned by the director of Columbia University’s Center for Infection and Immunity in New York – Dr. Ian Lipkin - who served as technical advisor for the film.

 

Bats, increasingly, are being viewed as substantial reservoirs for dangerous viruses. While long known to vector rabies, in the 1990s outbreaks of Hendra in Australia and Nipah in Malaysia and parts of Asia were eventually traced to bats, and while conclusive evidence is still lacking, the Ebola virus (and its cousin Marburg) are all believed to have bat origins

 

Bats are abundant (roughly 1/4th of all mammal species), mobile and wide ranging, and have adapted over millions of years to carry a variety of highly pathogenic viruses without ill effect.

Over the past couple of years we’ve also seen two new subtypes of influenza identified in bats (see A New Flu Comes Up To Bat & PLoS Pathogens: New World Bats Harbor Diverse Flu Strains).  All things considered, the past 20 years have been a Chiropterist’s delight.

 

While the world is riveted to the Ebola tragedy playing out in Africa, the bat viruses that with the most pandemic potential are those that once acquired, can spread via the respiratory route.  SARS and MERS are the two best known examples, but there are other similar coronaviruses circulating in bat that have the potential to jump species as well.

 

In September of 2012, shortly after the announced discovery of the MERS virus, I wrote that researchers from the University of Hong Kong had compared the genetic structure of the newly discovered coronavirus with other coronaviruses, and found it to be a 90% match to the HKU4 and HKU5 strains collected in the middle of the last decade in Hong Kong (see Coronavirus `Closely Related’ To HK Bat Strains.)

 

Earlier research (see Nature: Receptor For NCoV Found) determined that MERS-CoV uses a well known cell surface protein called dipeptidyl peptidase 4 (DPP4) to enter and infect human cells. 

 

This DPP4 cell surface protein (also called CD26) is evolutionarily conserved in other species, including bats, non-human primates, and other animals – all of which suggests that this virus might be able to infect a wide range of hosts. 

 

All of which serves as prelude to a new study, published yesterday in PNAS  that looks at the ability of the HKU4 coronavirus, and MERS-CoV, to attach to, and enter human cells. While both use the same dipeptidyl peptidase 4 (DPP4) receptor, the MERS coronavirus is far more adept at actually entering human cells than its HKU4 cousin.

 

 

Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus

Yang Yang, Lanying Du, Chang Liu, Lili Wang, Cuiqing Ma, Jian Tang, Ralph S. Baric, Shibo Jiang, and Fang Li

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) currently spreads in humans and causes ∼36% fatality in infected patients. Believed to have originated from bats, MERS-CoV is genetically related to bat coronaviruses HKU4 and HKU5. To understand how bat coronaviruses transmit to humans, we investigated the receptor usage and cell entry activity of the virus-surface spike proteins of HKU4 and HKU5.

We found that dipeptidyl peptidase 4 (DPP4), the receptor for MERS-CoV, is also the receptor for HKU4, but not HKU5.

Despite sharing a common receptor, MERS-CoV and HKU4 spikes demonstrated functional differences.

First, whereas MERS-CoV prefers human DPP4 over bat DPP4 as its receptor, HKU4 shows the opposite trend. Second, in the absence of exogenous proteases, both MERS-CoV and HKU4 spikes mediate pseudovirus entry into bat cells, whereas only MERS-CoV spike, but not HKU4 spike, mediates pseudovirus entry into human cells.

Thus, MERS-CoV, but not HKU4, has adapted to use human DPP4 and human cellular proteases for efficient human cell entry, contributing to the enhanced pathogenesis of MERS-CoV in humans. These results establish DPP4 as a functional receptor for HKU4 and host cellular proteases as a host range determinant for HKU4. They also suggest that DPP4-recognizing bat coronaviruses threaten human health because of their spikes’ capability to adapt to human cells for cross-species transmissions.

 

Although the full study is behind a pay wall, the University of Minnesota Academic Health Center has published the following press release with additional details.

 

UMN and NYBC research finds potential MERS transmission mechanism between bats and humans

(EXCERPTS)

Researchers have identified the mechanism used by the deadly MERS virus to transmit from bats to humans. Bats are a native reservoir for MERS and the finding could be critical for understanding the animal origins of the virus, as well as preventing and controlling the spread of MERS and related viruses in humans.

<SNIP>

Researchers have known the MERS virus infects human cells by attaching itself to a receptor molecule called dipeptidyl peptidase 4 (DPP4) and then entering human cells. However, it was not known how MERS was being transmitted from bats to humans.

"We wanted to better understand what prompted MERS to jump from bats to humans, and knew we needed to find a virus that was isolated in bats but had the potential to move into a human model," said Li. "HKU4 virus is related to MERS and has, so far, infected bats but not humans. It provided a good model for understanding the bat-to-human transmission process of MERS and related viruses."

After investigating both MERS and HKU4, researchers observed two major indicators MERS had adapted to human cells in a way HKU4 had not done yet.

The first discovery was that HKU4 virus recognizes the same receptor, DPP4, as MERS virus.. However, MERS virus uses the DPP4 molecule from human origin better, whereas HKU4 virus uses the DPP4 molecule from bat origin better. HKU4 also struggles to enter human cells once attached to the DPP4 receptor on the human cell surface. MERS does not have such a problem, though both viruses are able to enter bat cells.

"Overall, our findings suggest that MERS virus has successfully adapted to human cells for efficient infections, and HKU4 virus can potentially infect human cells," said Li. "MERS and MERS-related bat viruses present a constant and long-term threat to human health. So far little is known about these bat viruses that are evolutionary ancestors to human viruses. We need to look at bat viruses carefully, learn how they infect cells and jump species, and then develop strategies to block their transmission to humans."

For more on MERS, and its use of DPP4 receptors, you may wish to revisit:

Virology Journal: Bats, DPP4 Receptors, and MERS-CoV

EID Journal: Novel Bat Coronaviruses, Brazil and Mexico

Credit CDC Bat Safety

 

 

# 7610

 

All things considered, the past couple of decades have turned out to be busy ones for Chiroptologists (scientists who study bats). Increasingly these winged mammals are being viewed as naturals hosts for, and potential vectors of, a number of newly recognized emerging infectious diseases.

 

Long known for carrying rabies, over the past 20 years scientists have discovered that bats can also harbor such viral nasties as Marburg, Ebola, Nipah, Hendra, and a variety of coronaviruses (including SARS).

 

Quite surprisingly, in March of 2012, we also learned of a new H17 flu subtype – the first ever known to infect bats (see A New Flu Comes Up To Bat).

 

Last week’s discovery a of match to a segment of the MERS-CoV in a bat sample (see EID Journal: Detection Of MERS-CoV In Saudi Arabian Bat, once again points towards bats as being the likely animal host for an important emerging virus.

 

Yesterday the CDC’s EID Journal published a letter from researchers who sampled bats in Mexico and Brazil, and like similar studies in Europe, Africa, and Asia (see  EID Journal: EMC/2012–related Coronaviruses in Bats, Coronavirus `Closely Related’ To HK Bat Strains), they found a number novel coronaviruses among them.

While none were matches for either SARS or MER-CoV, notably one was a Betacoronavirus – as are MERS and SARS.  I’ve provided some excerpts below, but follow the link to read it in its entirety.

 

Letter

Novel Bat Coronaviruses, Brazil and Mexico

Luiz Gustavo Bentim Góes¹, Sicilene Gonzalez Ruvalcaba¹, Angélica Almeida Campos, Luzia Helena Queiroz, Cristiano de Carvalho, José Antonio Jerez, Edison Luiz Durigon, Luis Ignacio Iñiguez Dávalos, and Samuel R. Dominguez

 

To the Editor: Bats are now recognized as natural reservoirs for many families of viruses that can cross species barriers and cause emerging diseases of humans and animals. Protecting humans against emerging diseases relies on identifying natural reservoirs for such viruses and surveillance for host-jumping events.

 

The emergence of the Middle East respiratory syndrome coronavirus (MERS-CoV) on the Arabian Peninsula (1) further justifies increased surveillance for coronaviruses (CoVs) in bats. MERS-CoV most likely is a zoonotic virus from a bat reservoir and is associated with high case-fatality rates among humans.

 

The existence of a diverse array of alphacoronaviruses in bats in the United States, Canada, and Trinidad has been reported (2–6). Recently, a possible new alphacoronavirus was detected in an urban roost of bats in southern Brazil (7), and a survey of bats in southern Mexico reported 8 novel alphacoronaviruses and 4 novel betacoronaviruses, 1 with 96% similarity to MERS-CoV (8). These findings expand the diversity and range of known bat coronaviruses and increase the known reservoir for potential emerging zoonotic CoVs.

 

<SNIP>

 

In summary, we found a novel alphacoronavirus in bats from Brazil and a novel betacoronavirus in a bat from Mexico. Both viruses were detected in bats with known or potential contact with humans. Because the bats we sampled were mostly adult males, the prevalence of CoVs that we identified is probably an underestimation of the true incidence of CoVs in these bat populations.

 

For bats of other species, incidence of CoVs among juvenile and female bats is higher (2,9). Furthermore, we used a non-nested, broadly conserved CoV PCR, which might have limited the sensitivity of CoV RNA detection.

 

The finding of a novel betacoronavirus in insectivorous bats in the New World is noteworthy. Three human CoVs (229E, SARS-CoV, and MERS-CoV) all have animal reservoirs of closely related viruses in Old World insectivorous bats (10) from which they most likely emerged, either directly or indirectly, into the human population.

 

Ongoing surveillance for CoVs in wildlife and increased research efforts to better understand the factors associated with CoV host-switching events are warranted.

 

None of this is meant to demonize bats, as they play an important role in our ecosystem. However, bats are increasingly being associated with diseases deadly to humans. 

 

To learn how you can stay safe when bats are near, the CDC offers the following advice.

 

Take Caution When Bats Are Near

ECDC Comment On MERS-CoV Detection In A Bat

Credit Wikipedia

 

 

# 7608

 

The ECDC has published their comment on last week’s news (see EID Journal: Detection Of MERS-CoV In Saudi Arabian Bat) that Dr. Ian Lipkin’s lab at Columbia University had detected a match to the MERS virus in a bat.

 

As we’ve seen from other analyses of this study (see Branswell: A Deeper Look At Yesterday’s MERS-CoV In Bats Story), this author points out that the complete virus MERS virus was not recovered from these bat samples, but rather, a viral segment was sequenced and matched.

 

 

You can find additional commentary on scientific issues on the ECDC’s Scientific advice webpage.   Follow the link for the full report, including cites.

 

 

MERS CoV isolated in a bat

27 Aug 2013

A study published in the Centers for Disease Control and Prevention journal Emerging Infectious Diseases by Memish et al. analyzed the presence of coronaviruses (including MERS-CoV) in 1.003 samples from wild bats collected in October 2012 and April 2013 in Saudi Arabia. Samples were collected in Bisha, Saudi Arabia, close to where the first patient with MERS-CoV was identified in September 2012 and in other regions where MERS-CoV cases have been found. Multiple alpha and beta coronavirus sequences were identified in 220 out of 732 roost feces samples and seven of 91 rectal swab samples or fecal pellets. One amplified sequence of MERS-CoV from a T. perforatus bat captured in October 2012 in Bisha matched 100% with the MERS-CoV cloned from the index case-patient in Bisha.

 

The authors conclude that bats might play a role in human infection although this does not exclude the possibility of other hosts.

 

ECDC comment, 26 August 2013:

Identifying the host/s and source of MERS-CoV is urgently needed to prevent further infections and spread of the disease. Bat species are a well-known reservoir of coronaviruses and the study of Memish et al. confirms this.

 

While the results from the study are intriguing, there are several limitations that might limit a conclusion that bats are the direct source of MERS-CoV in humans. In this study a total of 1,003 different samples were collected from 110 bats captured during two samplings (October 2012 and April 2013); of those 227 samples tested positive for coronavirus, only one was found positive for the human MERS-CoV. The information about the viral load of the MERS-CoV positive sample is missing and the failure of further sequencing might lead to the speculation of a very low virus load in the sample.

 

The amplified bat MERS-CoV sequence was very short and lies within a conserved region of the genome, however a divergence within other genomic regions cannot be ruled out. Furthermore the MERS-CoV sequence amplification product of this positive sample was retrieved only from newly established generic MERS-Coronavirus (nested RdRp) assay, while the World Health Organization  recommended MERS-CoV specific assays were negative.

 

All coronavirus sequences were detected in fecal pellets or from roost feces but not from serum, throat swab samples, or urine. It is unclear if other samples from this particular MERS-CoV positive animal were also available and tested in this study.

 

The possibility of transmitting virus via faeces from bats to humans has been discussed for rabies (Gibbons 2002, Johnson, Phillpotts et al. 2006) and might also been a route of transmission for MERS-CoV. Just as people have been infected with hantavirus while sweeping-up dried mouse droppings  humans (and camels) could be infected by inhaling dust mixed with dried contaminated bat, or other animal, excrement (Jonsson, Figueiredo et al. 2010, Richardson, Kuenzi et al. 2013).

 

This, and the study of Reusken et al. (Reusken, Haagmans et al. 2013) cited in the ECDC Public Health Development of 12 August 2013, provide evidence that MERS-CoV might be a zoonotic disease but it is still not clear how the disease progresses from animals to humans. The epidemiological investigations excluded so far direct animal contact of most of the MERS-CoV patients as the probable route of infection but indirect mechanisms could be involved.

 

The previously published ECDC risk assessment is still valid.

(Continue . . . )

 

Branswell: A Deeper Look At Yesterday’s MERS-CoV In Bats Story

 

Credit Wikipedia

 

# 7593

 

Amid the flurry of reports yesterday we saw a high profile dispatch published in the EID Journal that announced the Detection Of MERS-CoV In Saudi Arabian Bat. 

 

A research team that included Saudi Deputy Health Minister Ziad A. Memish, Dr. Ian Lipkin’s team at Columbia University, and researchers from EcoHealth Alliance -  published they had found  a virus from a bat in Saudi Arabia that they called `A 100% genetic match’ to the MERS Coronavirus.

 

In yesterday’s blog , I cautioned that this was not a 100% match to the entire viral genome , but to a subsection of the virus.

 

Today the inimitable Helen Branswell provides far greater detail on how this match was made, what it does and does not mean, and includes comments from the corresponding author Dr. Ian Lipkin and from Andrew Rambaut, a professor of molecular evolution at the University of Edinburgh.

 

Follow the link to read:

 

Virus fragment from bat in Saudi Arabia perfect match for MERS virus: study

By Helen Branswell, The Canadian Press August 21, 2013

 

Highly recommended.

EID Journal: South African Bat Carries Close Relative To MERS-CoV

Coronavirus - Photo Credit WHO

 

 

# 7511

 

Yesterday the CDC’s EID journal published a letter from  researchers from Germany and South Africa who report detecting the closest relative yet to the MERS coronavirus in the feces of a bat sampled in South Africa – more than 3,000 miles from the outbreak in the Middle East.

 

Although bats have been tentatively linked to the MERS virus (see EID Journal: EMC/2012–related Coronaviruses in Bats & Coronavirus `Closely Related’ To HK Bat Strains) a really close match to MERS coronavirus has yet to be isolated from an animal host.

 

Many researchers also suspect that an intermediary host – one that amplifies the virus – may be involved in the chain of transmission leading to human infection as well.

 

Although not an exact match, and only isolated from one bat, this latest discovery points to another avenue of research in the hunt for the origins of this virus.

First, a link to the EID article, then some excerpts from the press release from the University of Bonn.

 

 

Volume 19, Number 10—October 2013

Letter

Close Relative of Human Middle East Respiratory Syndrome Coronavirus in Bat, South Africa

To the Editor: The severe acute respiratory syndrome (SARS) outbreak of 2002–03 and the subsequent implication of bats as reservoir hosts of the causative agent, a coronavirus (CoV), prompted numerous studies of bats and the viruses they harbor. A novel clade 2c betacoronavirus, termed Middle East respiratory syndrome (MERS)–CoV, was recently identified as the causative agent of a severe respiratory disease that is mainly affecting humans on the Arabian Peninsula (1).

Extending on previous work (2), we described European Pipistrellus bat–derived CoVs that are closely related to MERS-CoV (3). We now report the identification of a South Africa bat derived CoV that has an even closer phylogenetic relationship with MERS-CoV.

(Continue . . .)

 

 

 

University of Bonn

Does the dangerous new Middle East coronavirus have an African origin?

Researchers discover a close relative in South African bats

IMAGE: In this animal the scientists from the University Bonn (Germany) and from South Africa found a virus that ist genetically more closely related to MERS-CoV than any other known virus....

 

The MERS-coronavirus is regarded as a dangerous novel pathogen: Almost 50 people have died from infection with the virus since it was first discovered in 2012. To date all cases are connected with the Arabian peninsula. Scientists from the University Bonn (Germany) and South Africa have now detected a virus in the faeces of a South African bat that is genetically more closely related to MERS-CoV than any other known virus. The scientists therefore believe that African bats may play a role in the evolution of MERS-CoV predecessor viruses. Their results have just been published online in the journal "Emerging Infectious Diseases".

<SNIP>

A collaboration of researchers from the Institute of Virology at the University Bonn, Germany, the University of Stellenbosch and several other South African institutions have recently found evidence that MERS-CoV could possibly originate from bats occurring in southern Africa. The South African scientists, headed by Prof. Wolfgang Preiser, tested faecal material from a total of 62 bats from 13 different species for coronaviruses. In collaboration with their colleagues in Bonn, headed by Dr. Jan Felix Drexler, they investigated the genetic material of the viruses that they found.

 

In a faecal sample from a bat of the species Neoromicia cf. zuluensis they found a virus that is genetically more closely related to MERS-CoV than any other known virus. They believe that MERS-CoV may originally come from bats and may have reached the human population via other animals acting as intermediate hosts.

Search for MERS-CoV progenitor should include Africa

 

(Continue . . . )

 

ProMed Mail: Details On 10 Coronavirus Cases In Saudi Arabia

 

Photo Credit NIAID

 

# 7225

 

ProMed Mail has recently published two emails from Ziad Memish, Deputy Minister for Public Health for the Kingdom of Saudi Arabia, that outline – in far greater detail – the first 7 coronavirus cases reported yesterday – and adds 3 more to the list.

You’ll find the details, including commentary by ProMed Editors, at NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN (17): SAUDI ARABIA.

 

Subject: Urgent update on nCOV from KSA
----------------
The following is the summary of the 7 reported cases confirmed microbiologically as of yesterday [2 May 2013]. Prior information was based on preliminary testing both to WHO and the press; we now confirm the following results.

• Case 1: 59 y.o. male with multiple comorbidities. Date of onset of symptoms [14 Apr 2013] and passed away [19 Apr 2013].
• Case2: 24 y.o. male with multiple comorbidities. Date of symptoms [17 Apr 2013] and still in ICU in critical but stable condition.
• Case 3: 87 y.o. male with multiple comorbidities. Date of symptoms [17 Apr 2013] and passed away [28 Apr 2013].
• Case 4: 58 y.o. male with multiple comorbidities. Date of symptoms [22 Apr 2013] still in ICU in stable but critical condition.
• Case 5: 94 y.o. male with multiple comorbidities. Date of symptoms [22 Apr 2013] and passed away [26 Apr 2013].
• Case 6: 56 y.o. male with multiple comorbidities. Date of Symptoms [22 Apr 2013] and passed away [30 Apr 2013].
• Case 7: 56 y.o. male with multiple comorbidities. Date of symptoms [22 Apr 2013] and passed away [29 Apr 2013].
  

As the NFP for KSA you should know that the investigations are ongoing and include both testing and epidemiology investigations of family members and healthcare workers. So far we have not found symptomatic infection in any healthcare workers linked to these cases. Family investigations for 3 families are to be completed tomorrow [4 May 2013]; the others will be done as we gain access. Sensitivities around grieving are of course an issue.

Subject: Urgent update nCOV cluster KSA
-------------
This is a preliminary update on the status as of a few minutes ago. Three further cases have been discovered from the investigation which is still ongoing:

• Case 8: 53 y.o. female with comorbidities. Date of symptoms [27 Apr 2013] she is in stable but critical condition
• Case 9: 50 y.o. male with comorbidity. Date of symptoms [30 Apr 2013] with pneumonia and he is well on the inpatient ward.
• Case 10: 33 y.o. male with comorbidity. Family contact of a deceased patient. Date of symptoms [28 Apr 2013]. Inpatient in the medical ward and doing well.

As stated earlier our investigation of contacts and active screening of inpatients who fit case definition is ongoing.

 

Interestingly, 9 of the 10 cases here are male.  The ages range from 24 to 94.

 

Follow this link to read ProMed’s commentary about onset dates and speculation that this virus – like Nipah in Bangladesh – may be jumping to humans from bats that feed on dates.

 

Saudi Arabia is the world’s second largest producer of dates (following Egypt), and the date tree yields not only fruit, but palm leaves which are used to make many common items (hats, screens, baskets, brooms), along with date juice or syrup.

 

Some types of bats, which are a suspected vector of the novel coronavirus (see EID Journal: EMC/2012–related Coronaviruses in Bats & mBio: New Coronavirus Linked To Bats) are known to roost in the tops of date palm trees in the Middle East. 

 

Epidemiological investigations have fingered the consumption of raw (uncooked) date palm juice in Bangladesh as Nipah’s primary route into the human population.

 

The Nipah virus is carried by fruit bats of the Pteropodidae family, and their preference for roosting in the tops of trees rather than caves allows them to contaminate date juice collection jars with their virus laden urine and feces.

 

Date Palm Sap Collection – Credit FAO

Collection of date palm juice is a seasonal activity (December - May) in Bangladesh, and as you might expect, that time period also defines their Nipah season.

 

For more on the Nipah virus you may wish to revisit.

 

Bangladesh: Updating The Nipah Outbreak

Bangladesh: Nipah Update

Update: Hendra In Queensland, Nipah In Bangladesh

 

 

As far as the coronavirus goes - It is an interesting theory - but we’ll have to wait to see whether epidemiological investigations find any kind of solid connection.

A Hong Kong Civets Lesson

Credit Wikipedia

 

# 7018

 

 

Early epidemiological and serological investigations led many researchers to suspect that palm civets – small nocturnal mammals, a delicacy often served in Chinese `wild flavor’ restaurants – were a possible reservoir host for the SARS virus that erupted a decade ago in rural Guangdong Province.

 

This link first appeared in a World Health Organization  SARS update (#64 Situation in Toronto, detection of SARS-like virus in wild animals) on May 23rd, 2003 (excerpts follow):

 

Research teams in Hong Kong and Shenzhen, China have today announced the results of a joint study of wild animals taken from a market, in southern China, selling wild animals for human consumption.

The study detected several coronaviruses closely related genetically to the SARS coronavirus in two of the animal species tested (masked palm civet and racoon-dog). The study also found that one additional species (Chinese ferret badger) elicited antibodies against the SARS coronavirus. These and other wild animals are traditionally considered delicacies and are sold for human consumption in markets throughout southern China.

<SNIP>

Information on the potential role of animals in the transmission of SARS is important to overall understanding of SARS. Much more research is needed before any firm conclusions can be reached. At present, no evidence exists to suggest that these wild animal species play a significant role in the epidemiology of SARS outbreaks. However, it cannot be ruled out that these animals might have been a source of human infection.

 

This research, led by Dr. Guan Yi, led to the temporary ban on the sale of civets and the closing down of numerous wildlife markets across much of China.

 

 

While not conclusive, the case against palm civits grew stronger that fall with the publication of:

 

Isolation and characterization of viruses related to the SARS coronavirus from animals in southern China.

Guan Y, Zheng BJ, He YQ, Liu XL, Zhuang ZX, Cheung CL, Luo SW, Li PH, Zhang LJ, Guan YJ, Butt KM, Wong KL, Chan KW, Lim W, Shortridge KF, Yuen KY, Peiris JS, Poon LL.

Source

Department of Microbiology, The University of Hong Kong, University Pathology Building, Queen Mary Hospital, Hong Kong Special Administrative Region, People's Republic of China. yguan@hkucc.hku.hk

Abstract

A novel coronavirus (SCoV) is the etiological agent of severe acute respiratory syndrome (SARS). SCoV-like viruses were isolated from Himalayan palm civets found in a live-animal market in Guangdong, China. Evidence of virus infection was also detected in other animals (including a raccoon dog, Nyctereutes procyonoides) and in humans working at the same market. All the animal isolates retain a 29-nucleotide sequence that is not found in most human isolates. The detection of SCoV-like viruses in small, live wild mammals in a retail market indicates a route of interspecies transmission, although the natural reservoir is not known.

 

In January of 2004, when it looked as if SARS might be about to return, China undertook a massive cull of palm civets (see Time Magazine Averting an Outbreak by Karl Taro Greenfeld).

 

Over the next few years, however, the case against civets grew weaker, as more closely related SARS viruses were detected in bats – suggesting that civets were either secondary, intermediate, or perhaps even incidental hosts.

 

Bats, civets and the emergence of SARS

Curr Top Microbiol Immunol. 2007;315:325-44.

Wang LF, Eaton BT.

Abstract

Severe acute respiratory syndrome (SARS) was the first pandemic transmissible disease of previously unknown aetiology in the twenty-first century. Early epidemiologic investigations suggested an animal origin for SARS-CoV. Virological and serological studies indicated that masked palm civets ( Paguma larvata), together with two other wildlife animals, sampled from a live animal market were infected with SARS-CoV or a closely related virus.

 

Recently, horseshoe bats in the genus Rhinolophus have been identified as natural reservoir of SARS-like coronaviruses. Here, we review studies by different groups demonstrating that SARS-CoV succeeded in spillover from a wildlife reservoir (probably bats) to human population via an intermediate host(s) and that rapid virus evolution played a key role in the adaptation of SARS-CoVs in at least two nonreservoir species within a short period.

 

 

Since 2007, the case against bats has grown stronger, while the case against civets has become less so. In recent months we’ve seen bats linked to another, emerging coronavirus (see EID Journal: EMC/2012–related Coronaviruses in Bats) out of the Middle East.

 

This emergent novel coronavirus (dubbed NCoV by the WHO), has public health agencies around the world on high alert (see  WHO: Revised NCoV Surveillance Recommendations), although to date only 15 cases have been identified. 

 

Nowhere is this more apparent than in Hong Kong – arguably the city hardest hit by SARS epidemic in 2003 (see SARS And Remembrance) – where their Centre for Health Protection is taking an aggressive, and very public stance against this new viral threat.

 

While the link between civets and SARS has been diluted over time, the fact is we don’t have a good handle yet on the emerging NCoV.  On Monday of this week a WHO update described our knowledge gap this way:

 

A number of unanswered questions remain, including the virus reservoir, the means by which seemingly sporadic infections are being acquired, the mode of transmission between infected persons, the clinical spectrum of infection and the incubation period.

 

Given this current dearth of knowledge, overnight Hong Kong announced that their longstanding ban against importing civets remains in place, and that a new ban on importing bats is going into effect. 

 

This from http://www.info.gov.hk.

 

HK continues import ban on game civet cats

The Centre for Food Safety (CFS) of the Food and Environmental Hygiene Department today (March 21) reminded the public that the import of game masked palm civets (also known as Himalayan palm civets or gem-faced civets, or commonly referred to as civet cats) is prohibited.

 

A spokesman for the CFS said that the import ban on masked palm civets was introduced as a precautionary measure after the outbreak of SARS (Severe Acute Respiratory Syndrome) in 2003 by the Director of Food and Environmental Hygiene.

The spokesman said, "The Government has remained vigilant ever since. We see no justification for relaxing the control."

 

He pointed out that the import ban would also extend to bats due to the public health threat from novel coronavirus.

 

No application for importing of the above products had been received over the past decade.

 

He called on members of the public to exercise caution when contacting, handling or eating wild animals to minimise the risk of zoonotic diseases.

 

"We will closely monitor the situation and remain vigilant on the latest developments," the spokesman added.

Ends/Thursday, March 21, 2013
Issued at HKT 16:01

 

 

Ten years after the SARS epidemic began, there are still many unanswered questions regarding its origins. 

 

Only six months after NCoV was first detected in a patient from Saudi Arabia, it is not surprising that we still know so very little about its place in the natural environment.

 

Since we don’t know at this stage how much of a threat NCoV may ultimately provide, public health agencies are obliged to take whatever prudent steps they can to prevent the spread or importation of this, or any other emergent threat.

 

Because they know that the old adage is true.

 

`When public health works, nothing happens.’

Queensland: Rare Australian Bat Lyssavirus Infection

Fruitbats In Australia – Credit Wikipedia

 

 

# 6939

 

 

Rabies - the best known of the Lyssaviruses - is believed responsible for roughly 55,000 deaths each year around the world.  

 

According to the World Health Organization rabies FAQ,  ` . . . rabies still poses a significant public health problem in many countries in Asia and Africa where 95% of human deaths occur even though safe, effective vaccines for both human and veterinary use exist’.

 

In Greek mythology, Lyssa was the Goddess of rage or madness, hence the adoption of name Lyssavirus for the genus that includes rabies, and others including the Australian bat lyssavirus (ABLV), Duvenhage virus, European bat lyssaviruses 1 and 2, and Lagos bat virus.

 

Australia is somewhat unique in that it is one of the few regions in the world where rabies has never been detected.  Others include New Zealand, Iceland, and the Hawaiian islands, while elsewhere rabies has been eliminated in a number of other countries.

 

Australia does have Australian Bat Lyssavirus (ABLV), which is a close cousin to the rabies virus.

First identified in 1996, ABLV is known to be carried by at least four varieties of flying foxes/fruit bats and one species of insectivore microbat in Australia (see MMWR  1996 Dispatch Encephalitis Caused by a Lyssavirus in Fruit Bats in Australia).

 

Up until this past week, only two human infections with ABLV have been reported, both fatal, and both in Queensland.  In one of those cases, symptoms did not appear until two years after the bat exposure, a phenomenon that has rarely been reported with rabies as well.

 

This week, we learn of a third case, an 8-year old boy who is in a coma in a Queensland hospital.

 

 

Queensland child critical after contracting deadly bat lyssavirus

• From: AAP
• February 15, 2013 3:28PM

AN eight-year-old Queensland boy is critically ill with a bat-borne virus that causes fits, paralysis and death.

 

(Continue . . .)

 

 

According to this article, this latest case, on top of the infrequent outbreaks of Hendra virus (see Queensland: A Hendra Watch & A New Vaccine) has already led to renewed calls for the culling of bats, a highly divisive topic in Australia.

 

There are many who fear that the indiscriminate culling of bats would simply increase human exposure to bat-borne viruses, and the loss of native bats could upset the ecological balance.

 

For now, the Australian government advises:

 

The best protection against being exposed to the virus is for members of the community to avoid handling any bat or flying fox.

 

The Australian Government’s Immunization Handbook has some extensive information on ABLV, its prophylaxis, and treatment.

 

3.1 Australian bat lyssavirus infection and rabies

Virology

Australian bat lyssavirus (ABL) and rabies virus are members of the family Rhabdoviridae, genus Lyssavirus. There are 7 known genotypes within the genus Lyssavirus; ABL (genotype 7) is more closely related to rabies virus (genotype 1) than any of the other 6 genotypes.

Clinical features

Based on the 2 recognised human cases of ABL infection, it has to be assumed that ABL has the same clinical features as rabies. The incubation period of rabies is usually 3 to 8 weeks, but can range from as short as a week to, on rare occasions, several years. The risk of rabies is higher, and the incubation period shorter, after severe and multiple wounds proximate to the central nervous system (such as on the head and neck) and in richly innervated sites (such as the fingers).

Typically, in the prodromal phase of rabies, which lasts up to 10 days, the patient may experience non-specific symptoms such as anorexia, cough, fever, headache, myalgia, nausea, sore throat, tiredness and vomiting. Paraesthesiae and/or fasciculations at or near the site of the wound may be present at this stage. Anxiety, agitation and apprehension may also occur.

Most rabies patients present with the furious or encephalitic form. In the encephalitic phase, objective signs of nervous system involvement include aerophobia, hydrophobia, bizarre behaviour, disorientation and hyperactivity. Signs of autonomic instability such as hypersalivation, hyperthermia and hyperventilation may occur.

 

The neurological status of the patient deteriorates over a period of up to 12 days, and the patient either dies abruptly from cardiac or respiratory arrest, or lapses into a coma. Rabies is almost invariably fatal.

Epidemiology

Rabies is endemic throughout much of Africa, Asia, the Americas and Europe, where the virus is maintained in certain species of mammals.

Australia, New Zealand, Japan, Papua New Guinea and Pacific Island nations are free of endemic rabies but it must be remembered that this can change at any time. For example in 2008, rabies was reported in dogs on the island of Bali, Indonesia. Prior to this, Bali was considered to be free of rabies although rabies was known to occur in other areas of Indonesia. Human rabies characteristically follows a bite from a rabid animal, most frequently a dog, but in some parts of the world, other animals, such as jackals and bats, are important sources of exposure. In countries where rabies vaccination of domestic animals is widespread (North America and Europe), wild animals such as raccoons and foxes are important reservoirs.

Cases of rabies after animal scratches, the licking of open wounds or saliva contact with intact mucous membranes are very rare. Cases have been recorded after exposure to aerosols in a laboratory and in caves infested with rabid bats, and cases have been reported following tissue transplantation from donors who died with undiagnosed rabies.

(SNIP)

In Australia, 2 cases of a fatal rabies-like illness caused by ABL have been reported, one in 1996 and the other in 1998.6 Both patients had been bitten by bats. Evidence of ABL infection has since been identified in all 4 species of Australian fruit bats (flying foxes) and in several species of Australian insectivorous bats. It should therefore be assumed that all Australian bats have the potential to be infected with ABL.

EID Journal: EMC/2012–related Coronaviruses in Bats

 

Photo Credit NIAID

 

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Yesterday, in EID Journal: Ebola Virus Antibodies From Bats In Bangladesh, we looked at the possible carriage of the Ebola virus in Asian bats, and reviewed some of the history of emerging zoonotic diseases that can be carried by these winged mammals.

 

Today,we have another Chiropterist’s delight, an EID Journal dispatch that reports on the presence of betacoronaviruses – similar to the ones that infected a small number of people in the Middle East last year – among bats sampled in Ghana, and across four European nations.

 

First, a brief review of the outbreak of this novel coronavirus, which began in April of 2012.  This from the World Health Organization.

 

Background and summary of novel coronavirus infection – as of 21 December 2012

Over the past three months, WHO has received reports of nine cases of human infection with a novel coronavirus. Coronaviruses are a large family of viruses; different members of this family cause illness in humans and animals. In humans, these illnesses range from the common cold to infection with Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS CoV).

 

This summary provides the latest information on all reported cases and provides details of a WHO mission to Jordan, which has concluded since the last web update.

 

Thus far, the laboratory confirmed cases have been reported by Qatar (two cases), Saudi Arabia (five cases) and Jordan (two cases). All patients were severely ill, and five have died.

 

<SNIP>

 

WHO recognizes that the emergence of a new coronavirus capable of causing severe disease raises concerns because of experience with SARS. Although this novel coronavirus is distantly related to the SARS CoV, they are different. Based on current information, it does not appear to transmit easily or sustainably between people, unlike the SARS virus.

(Continue . . . )

 

 

While we’ve not seen any new reports of illness from this virus in several months, the memories of the SARS outbreak in 2002-2003 remain fresh. Although this new Coronavirus (dubbed Human Betacoronavirus EMC/2012) isn’t SARS, it does come from the same family.

 

Last September, in Coronavirus `Closely Related’ To HK Bat Strains, we looked at research from the University of Hong Kong that compared the genetic structure of this newly discovered coronavirus with other coronaviruses, and found it to be a 90% match to the HKU4 and HKU5 strains collected in the middle of the last decade in Hong Kong.

Since then we’ve seen additional evidence suggesting that bats are likely this virus’s natural reservoir in mBio: New Coronavirus Linked To Bats and mBio: Coronavirus Has An Affinity For Multiple Hosts.

 

But so far, the viruses found in bats have been similar, but not a really close match to the HCOV EMC/2012 virus.

 

In an EID Journal dispatch published today, we get word of the closest match to date between this mystery-shrouded emerging coronavirus, and viruses identified in bats.

 

First the link and abstract (or follow the link to read it in its entirety), then I’ll return with a summation.

 

Human Betacoronavirus 2c EMC/2012–related Viruses in Bats, Ghana and Europe

Augustina Annan, Heather J. Baldwin, Victor Max Corman, Stefan M. Klose, Michael Owusu, Evans Ewald Nkrumah, Ebenezer Kofi Badu, Priscilla Anti, Olivia Agbenyega, Benjamin Meyer, Samuel Oppong, Yaw Adu Sarkodie, Elisabeth K.V. Kalko, Peter H.C. Lina, Elena V. Godlevska, Chantal Reusken, Antje Seebens, Florian Gloza-Rausch, Peter Vallo, Marco Tschapka, Christian Drosten, and Jan Felix Drexler

Abstract

We screened fecal specimens of 4,758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9%) of 185 Nycteris bats and 40 (14.7%) of 272 Pipistrellus bats. Their genetic relatedness indicated EMC/2012 originated from bats.

 

The entire report is much longer, and quite detailed, but briefly:

 

Fecal specimens were collected from 14 bat species from 7 locations across Ghana and 5 areas in Germany, the Netherlands, Romania, and Ukraine, and analyzed for the presence of HCOV EMC/2012-like viruses using nested reverse transcription PCR (RT-PCR). 

 

Previously, 2c bat CoVs have only been detected in vespertilionid bats, but in Ghana they detected related viruses in Nycteris bats as well. While similar to the HCOV EMC/2012 virus, they were from a genetically distinct group. 

 

The authors write:

 

This novel Nycteris bat CoV differed from the 2c-prototype viruses HKU4 and HKU5 by 8.8%–9.6% and from EMC/2012 by 7.5% and thus constituted a novel RGU.

 

In 2008 a bat coronavirus was identified in the Netherlands called VM314 that partial sequencing has shown to be fairly closely related to HCOV EMC/2012.

 

In examining 272 P. pipistrellus, P. nathusii, and P. pygmaeus bats from the Netherlands, Romania, and Ukraine they found 14% carried coronaviruses that were closely related to VM314.

The authors write:

 

The VM314-associated Pipistrellus bat betacoronaviruses differed from EMC/2012 by 1.8%. The difference between EMC/2012 and HKU5 was 5.5%–5.9%.

 

In summary, HKU5, EMC/2012, and the VM314-associated clade form 1 RGU according to our classification system, and the VM314-Pipistrellus bat clade contains the closest relatives of EMC/2012.

 

HKU4 and the Nycteris CoV define 2 separate tentative species in close equidistant relationship.

 

After calling for surveillance and screening of bats in the Middle East where these scattered human infections have been documented, the authors conclude:

The genomic data suggest that EMC/2012, like hCoV-229E and SARS-CoV, might be another human CoV for which an animal reservoir of closely related viruses could exist in Old World insectivorous bats(4,9).

 

Whether cross-order (e.g., chiropteran, carnivore, primate) host switches, such as suspected for SARS-CoV, have occurred for 2c clade bat CoVs remains unknown.

 

However, we showed previously that CoVs are massively amplified in bat maternity colonies in temperate climates (13). This amplification also might apply to the Nycteris bat CoV because, as shown previously for vespertilionid bats from temperate climates (14), detection rates of CoV are significantly higher among juvenile and lactating Nycteris bats.

 

In light of the observed high virus concentrations, the use of water from bat caves and bat guano as fertilizer for farming and the hunting of bats as wild game throughout Africa (15) may facilitate host switching events.

 

To our knowledge, no CoV has been isolated directly from bats. Further studies should still include attempts to isolate full virus genomes and to identify virulence factors that might contribute to the high pathogenicity of EMC/2012 (7).

EID Journal: Ebola Virus Antibodies From Bats In Bangladesh

Common pipistrelle (Pipistrellus pipistrellus) – Credit Wikipedia

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Several months ago in a blog called Virology Journal: Ebola Virus In Chinese Bats, we looked at the first evidence suggesting that Ebola viruses are circulating among bats in China, although the exact strain involved wasn’t clear.

 

Researchers were able to detect cross-reactive antibodies to two types of Ebola viruses (Zaire and Reston), but identification of the exact EBOV strain in China was not possible.

 

The natural reservoir for Ebola viruses are believed to be fruit bats of the Pteropodidae family, although the virus in humans is usually linked to the consumption of infected bushmeat (considered an intermediate host).

 

There are currently five known strains of the Ebola virus - Ebola-Zaire, Ebola-Sudan, Ebola-Reston, Ebola-Ivory Coast and Ebola-Bundibugyo – which along with a close cousin - the Marburg virus - make up the family Filoviridae.

 

Of these, only Ebola-Reston – found primarily in the Philippines – does not cause illness in humans.

 

Up until recently, Ebola Reston was the only ebolavirus thought to circulate outside of Africa.

 

Today, the CDC’s EID JOURNAL published a Dispatch that describes the seroprevalence of cross reactive antibodies against Ebola in bats tested in Bangladesh. A few excerpts, but follow the link to read the dispatch in its entirety.

 

Volume 19, Number 2—February 2013

Dispatch

Ebola Virus Antibodies in Fruit Bats, Bangladesh

Kevin J. Olival , Ariful Islam, Meng Yu, Simon J. Anthony, Jonathan H. Epstein, Shahneaz Ali Khan, Salah Uddin Khan, Gary Crameri, Lin-Fa Wang, W. Ian Lipkin, Stephen P. Luby, and Peter Daszak

Abstract

To determine geographic range for Ebola virus, we tested 276 bats in Bangladesh. Five (3.5%) bats were positive for antibodies against Ebola Zaire and Reston viruses; no virus was detected by PCR. These bats might be a reservoir for Ebola or Ebola-like viruses, and extend the range of filoviruses to mainland Asia.

<SNIP>

Conclusions

Our study provides evidence of Ebola virus infection in wildlife from mainland Asia and corroborates the observation that filoviruses are harbored across a much larger geographic range then assumed (2). Preferential reactivity to ZEBOV suggests exposure to an Ebola virus that is distinct from REBOV, the only filovirus currently found in Asia. We consider the likelihood of cross-reactivity with MARV as low because there is only a 35% aa identity between nucleoprotein genes of REBOV/ZEBOV and MARV. However, we cannot rule out co-infection with multiple filoviruses.

(Continue . . . )

 

An interesting side note, one of the authors listed on this dispatch is Professor Ian Lipkin, director of Columbia University’s Center for Infection and Immunity in New York. 

 

Dr. Lipkin served as technical advisor for the  2011 film Contagion, and created the fictional MEV-1 bat virus used as the movie’s viral villain  (see The Scientific Plausibility of `Contagion’).

 

Our knowledge of the diseases carried by bats has expanded considerably since the early 1990s. Up until that time, the primary concern was rabies.  

 

During the 1990s – two new bat-borne viruses emerged - Nipah and Hendra - both henipaviruses of the family Paramyxoviridae.

 

The Hendra virus was first isolated in 1994 after the deaths of 13 horses and a trainer in Hendra, a suburb of Brisbane, Australia. A stable hand, who also cared for the horses, was hospitalized, but survived.

 

Over the past 18 years 40 outbreaks of Hendra virus – all involving horses – have been reported in Australia. Four human fatalities have been linked to the virus as well.

 

 

The debut of Nipah was in Malaysia in 1998, where the virus first jumped from bats to local swine herds, probably via bat droppings into the swine’s environment or food. From there, it jumped to humans, resulting in 265 cases of acute encephalitis and more than 100 deaths (cite).

 

This first human outbreak was initially thought to be due to Japanese encephalitis, and so precautions around pigs were delayed for nearly two months, allowing the virus to spread.

 

Over the past decade, Nipah has sparked a number of small outbreaks across Southern Asia, although the most intense activity has been centered around Bangladesh.

 

Nipah/Hendra Virus & Fruit Bat Home Range – WHO

 

The most notorious of the emerging bat-viruses has been  SARS-CoV (coronavirus), which sparked an epidemic in 2002-2003 that infected roughly 8,000 people around the globe, killing nearly 800.

 

Which explains why so much interest has been paid to the detection last year of a handful of novel coronavirus infections in the Middle East (see WHO Coronavirus Update).

 

And perhaps most surprisingly of all, early in 2012 we learned about a new strain of influenza found in an unusual host: bats (see A New Flu Comes Up To Bat).

 

This discovery adds an H17 flu subtype, and a new host species, suddenly making all of the textbooks and slide presentations on influenza out of date.

 

In 2007 a PNAS article called A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans, told of a 39 year old man infected when a bat flew into their Malaysian home.  More than a week after he was placed in isolation, two other members of his family came down with the same illness, suggesting H-2-H transmission. 

 

The authors of that report wrote:

 

Bats, probably the most abundant, diverse, and geographically dispersed vertebrates on earth, have recently been shown to be the reservoir hosts of a variety of zoonotic viruses responsible for severe human disease outbreaks, some with very high mortality.

 

While most researchers expect the next pandemic to come from a swine or avian source, other species – like bats – are increasingly being looked to as significant reservoirs of dangerous zoonotic pathogens.

 

All of which makes studies, like this one today, of particular interested to researchers.

Bats, Viruses, And Their Immune Response

Common pipistrelle (Pipistrellus pipistrellus) – Credit Wikipedia

 

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For virologists and chiroptologists, an enduring mystery has been how bats are able to carry – without apparent ill effect – viruses that are normally deadly to most other mammals.

 

Long known for carrying rabies, over the past two decades we’ve discovered that bats can also harbor viruses such as Ebola, Marburg, Nipah, Hendra, and a variety of coronaviruses (including SARS). 

 

This week, in an article that appears in the Journal Science, we learn that some of the evolutionary changes that enable the bat to be the only mammal that can fly, may also help them to carry deadly viruses.

 

First a link to the Abstract (the whole paper is behind a pay wall), then excerpts from a Reuter’s news article that help flesh out the findings.

 

Published Online December 20 2012
< Science Express Index

Science DOI: 10.1126/science.1230835

• Report

Comparative Analysis of Bat Genomes Provides Insight into the Evolution of Flight and Immunity

Guojie Zhang, Christopher Cowled, Zhengli Shi, Zhiyong Huang, Kimberly A. Bishop-Lilly, Xiaodong Fang, James W. Wynne, Zhiqiang Xiong, Michelle L. Baker, Wei Zhao, Mary Tachedjian, Yabing Zhu, Peng Zhou, Xuanting Jiang, Justin Ng, Lan Yang, Lijun Wu, Jin Xiao, Yue Feng, Yuanxin Chen, Xiaoqing Sun, Yong Zhang, Glenn A. Marsh, Gary Crameri, Christopher C. Broder, Kenneth G. Frey, Lin-Fa Wang, Jun Wang

Abstract

Bats are the only mammals capable of sustained flight and are notorious reservoir hosts for some of the world’s most highly pathogenic viruses, including Nipah, Hendra, Ebola, and severe acute respiratory syndrome (SARS). To identify genetic changes associated with the development of bat-specific traits, we performed whole-genome sequencing and comparative analyses of two distantly related bat species, fruit bat Pteropus alecto and insectivorous Myotis davidii.

 

We discovered an unexpected concentration of positively selected genes in the DNA damage checkpoint and nuclear factor–κB pathways that may be related to the origin of flight, as well as expansion and contraction of important gene families. Comparison of bat genomes with other mammalian species has provided new insights into bat biology and evolution.

 

 

Admittedly, there is not much specificity in this abstract. 

 

Luckily, Tan Ee Lyn - Asia Health correspondent for Reuters – has an interview with the lead author -Professor Lin-Fa Wang, who reveals that some genetic changes necessary for flight may also help to moderate dangerous out-of-control immune responses known as Cytokine Storms.

Cytokines are a category of signaling molecules – proteins – that are released by immune cells that have encountered a pathogen, and are designed to alert and activate other immune cells to join in the fight against the invading pathogen.

 

Although poorly understood, the theory behind a `cytokine storm’ is this signaling process spirals out of control, resulting in an overwhelming immune response that can potentially kill the host.

 

According to Professor Lin-Fa Wang, this built-in suppression of the inflammatory (cytokine) response may be behind the bat’s unusual longevity (20 to 40 years), and their ability to `handle’ infection by normally deadly viruses.

 

 

Long-lived bats offer clues on diseases, aging

December 21, 2012 12:52 PM

HONG KONG: The bat, a reservoir for viruses like Ebola, SARS and Nipah, has for decades stumped scientists trying to figure out how it is immune to many deadly bugs but a recent study into its genes may finally shed some light, scientists said on Friday.Studying the DNA of two distant bat species,...

(Continue . . . )

 

 

In another article, this time in The Asian Scientist, the author talks about practical applications of this research, and is quoted as saying, “Our findings highlight the potential of using bats as a model system to study infection control, tumor biology, and the mechanisms of aging,”

 

 

Bats’ Immunity Against Deadly Viruses Linked To Their Ability To Fly

AsianScientist (Dec. 21, 2012) – An international team led by an infectious disease expert, Professor Lin-Fa Wang, at the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore has found that the evolution of flight in bats may have contributed to the development of a highly effective immune system, allowing bats to harbor some of the world’s deadliest viruses such as Ebola and SARS.

(Continue . . . )

 

Both news articles are worth reading in their entirety.

 

For more on cytokine storms, and how they may affect pandemic influenza mortality, you may wish to revisit some of these earlier blogs.

 

Study: Calming The Cytokine Storm

Cytokine Storm Warnings

The Baskin Influenza Pathogenesis Study

Pt. 1   Pt. 2   Pt. 3

Queensland: A Hendra Watch & A New Vaccine

Nipah/Hendra Virus & Fruit Bat Home Range – WHO

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Although long known to carry rabies, over the past two decades bats have increasingly been linked to emerging infectious diseases.

 

The SARS-CoV (coronavirus) outbreak of 2002-2003 – which infected roughly 8,000 people and killed nearly 800 – is undoubtedly the best known of these diseases, but is by no means the only one to emerge.

 

Genetic analysis of two recent novel coronavirus infections in the Middle East suggest (but fall short of proving) that bats may be the primary host for this virus as well (see Coronavirus `Closely Related’ To HK Bat Strains).

 

And the natural reservoir for the Ebola viruses (including Marburg) are believed to be fruit bats of the Pteropodidae family.

 

Prior to the SARS outbreak - during the 1990s – two new bat-borne viruses made headlines; Nipah and Hendra, both henipaviruses of the family Paramyxoviridae.

 

Of the two, Nipah has been the deadliest, causing outbreaks primarily in India and Bangladesh. But the virus was first discovered in April of 1999 when an outbreak occurred at a pig farm in Malaysia. 

 

During this initial outbreak, the virus jumped to local swine herds from bats, and infected more than 250 people, killing more than 100. The virus was then exported via live pigs to Singapore, where 11 more people died (see MMWR Update: Outbreak of Nipah Virus -- Malaysia and Singapore, 1999)

 

Over the past decade, Nipah has sparked a hand full of smaller outbreaks across Southern Asia with the greatest activity centered around Northern India and Bangladesh. Fruit bats (Pteropodidae) are considered the natural host of Nipah virus.

 

Perhaps most concerning has been evidence of limited nosocomial, or human-to-human transmission, of the Nipah virus (see Bangladesh: Updating The Nipah Outbreak).

 

The Nipah virus, like it’s close cousin the Hendra virus, is classified as a biosecurity level 4 (BSL-4) agent.

 

While not associated with as many human fatalities, the Hendra virus was first identified after the deaths of 13 horses and a trainer in Hendra, a suburb of Brisbane, Australia in 1994. A stable hand, who also cared for the horses, was hospitalized, but survived.

 

Another outbreak was later identified as having taken place in MacKay, 1000 km to the north of Brisbane, the previous month. Two horses died, and the owner was hospitalized several weeks later with meningitis. He recovered, but developed neurological symptoms and died 14 months later.

 

Over the past 18 years 40 outbreaks of Hendra virus – all involving horses – have been reported in Australia. Four human fatalities have been linked to the virus as well.

 

Subsequent studies have showed a high prevalence of the newly identified Hendra virus in Pteropid fruit bats (flying foxes) in the region.

 

Unlike Nipah, to date no human-to-human transmission of Hendra has been documented.

All of which brings us to the latest outbreak news, and hope for a new vaccine for horses that just became available. First stop, an update from the QLD Department of Agriculture, Fisheries, and Forestry.

 

November 2012

---

Hendra virus communique no.10-5 November 2012

Hendra virus incident Ingham

Biosecurity Queensland is managing a Hendra virus incident in Ingham after a positive test result was received on Friday 2 November 2012.

 

A mare was first noticed unwell on Wednesday 31 October 2012 by her owner. She was not interested in food, had a slight nasal discharge, rapid, laboured breathing, elevated heart rate, lowered head and was unsteady on her feet.

 

A private veterinarian visited the horse and collected samples for Hendra virus testing. The horse deteriorated and went down and was euthanased on Thursday 1 November 2012.

Movement restrictions

Biosecurity Queensland has quarantined the property and undertaken tracing and risk assessments to determine susceptible animals that may have had exposure to the virus.

 

There are eight horses remaining on the property as well as dogs and cats. Several rounds of testing will be conducted on animals assessed to be at risk of being exposed to Hendra virus before the quarantine can be lifted.

 

Restrictions will apply to moving horses and horse materials on and off the infected property, and the property will be quarantined for at least one month. There are no other movement restrictions for the general Queensland horse population because of Hendra virus.

Hendra virus vaccine

A commercial pharmaceutical company has released a Hendra virus vaccine for use in horses under a Minor Use Permit. Under permit conditions, only accredited veterinarians can administer the vaccine.

 

The vaccine provides another option for the horse industry to reduce the risk of Hendra virus infection; however it is important to remember no vaccine is 100% effective and people in contact with horses need to continue to practice good biosecurity and hygiene measures even if horses are vaccinated.

 

Horse owners should discuss with their veterinarian whether vaccinating their horse is appropriate.

 

From CSIRO (Commonwealth Scientific and Industrial Research Organisation) we get more details on this newly available vaccine, via a 9 minute audio podcast & transcript.

 

Vaccine for killer Hendra virus launched

Australian horse owners and the equine industry have received an important boost in their fight against the deadly Hendra virus with the introduction of Equivac® HeV vaccine. (9:02)

• 1 November 2012

 

 

A final note, in the QLD notice above, it mentions that dogs and cats are quarantined, as well as horses. This comes about primarily because in 2011, we saw the first evidence of canine infection with the virus (see Australia: Dog Tests Positive For Hendra Virus).

 

The Queensland DAFF maintains a FAQ file on Hendra and dogs, where they write:

 

What animals have been shown to get Hendra virus?

Naturally occurring infection is limited to horses, flying foxes, humans and dogs. In animals, naturally occurring clinical disease is limited to horses.

 

Hendra virus is present in wild flying fox populations but does not appear to cause disease in them.

Laboratory studies have shown that other species including cats, guinea pigs, ferrets and pigs can develop disease when inoculated with Hendra virus in an experimental setting. Other species, including rabbits and dogs, have developed antibodies to Hendra virus in an experimental setting, but did not develop any signs of illness.

 

Although transmission from animals other than horses to humans has not been demonstrated, it is always a concern whenever a virus adapts to or jumps to a new host.

 

It not only gives the pathogen fresh opportunities to mutate and evolve, it provides another potential vector to spread the disease.

 

And when that host is a dog or a cat – animals with whom humans closely interact – it naturally serves to increases those concerns.