Virology: Pathogenesis Of Avian A/H5N8 In Ferrets

 

# 9836

 

Despite being closely related to avian virus subtypes (H5N1, H5N6) that have produced serious morbidity and mortality in humans, the recently emerged H5N8 virus which has spread to both Europe and North America (see EID Journal: Novel Eurasian HPAI A H5 Viruses in Wild Birds – Washington, USA)  has never been linked to human infection or illness. 

Although not currently considered a serious threat to human health threat, the CDC has issued specific guidance documents for dealing with those who may have been exposed (see CDC Interim Guidance For Testing For Novel Flu & CDC Interim Guidance On Antiviral Chemoprophylaxis For Persons With Exposure To Avian Flu).

 

Despite the reassuring anecdotal data to date, it is important to understand the pathogenesis of this virus in birds and mammals, with an eye towards understanding how the threat may change over time.  

 

While humans have been so far unaffected, we have seen reports of dogs being infected with H5N8 (see MAFRA: H5N8 Antibodies Detected In South Korean Dogs (Again)).   The ability to infect canines does not automatically make it a human threat, but it does raise some concerns (see Study: Dogs As Potential `Mixing Vessels’ For Influenza).

 

Although not perfect, ferrets are considered a reasonable mammalian substitute for humans when testing respiratory viruses because their lung physiology is similar, and because they cough and sneeze when infected, very much as humans do.

 

All of which brings us to a new study (most of which, alas, is behind a pay wall) that looks at the pathogenesis of two Korean strains of H5N8 challenged ferrets.  What we can tell from the abstract, however, is that ferrets intranasally inoculated suffered no mortality or serious respiratory symptoms, but that ferrets intratracheally infected with one of the H5N8 strains showed `dose-dependent mortality’.

 

Pathogenesis of novel reassortant avian influenza virus A (H5N8) Isolates in the ferret 

Heui Man Kim^{1, 2,} , Chi-Kyeong Kim^{1, 3,} , Nam-Joo Lee, Hyuk Chu, Chun Kang, Kisoon Kim, Joo-Yeon Lee^,

doi:10.1016/j.virol.2015.02.042

---

Highlights

•  Outbreaks of HAPI H5N8 occurred in 2014, and spread to poultry farms in Korea.

• We evaluated the pathogenesis of H5N8 viruses in ferrets.

• Two Korean H5N8 strains did not induce mortality in intranasal challenged ferrets.

---

Abstract

Outbreaks of avian influenza virus H5N8 first occurred in 2014, and spread to poultry farms in Korea. Although there was no report of human infection by this subtype, it has the potential to threaten human public health. Therefore, we evaluated the pathogenesis of H5N8 viruses in ferrets. Two representative Korean H5N8 strains did not induce mortality and significant respiratory signs after an intranasal challenge in ferrets. However, ferrets intratracheally infected with A/broiler duck/Korea/Buan2/2014 virus showed dose-dependent mortality. Although the Korean H5N8 strains were classified as the HPAI virus, possessing multiple basic amino acids in the cleavage site of the hemagglutinin sequence, they did not produce pathogenesis in ferrets challenged intranasally, similar to the natural infection route. These results could be useful for public health by providing the pathogenic characterization of H5N8 viruses.

 

While it isn’t easy to infect a ferret, apparently if you provide a high enough dose, and place it far enough down the respiratory tract, it is possible.  Whether these same (unlikely to occur) conditions would elicit the same response in humans is unknown, but it is possible.

 
Although it is tempting to relegate H5N8 to the `only a threat to poultry’ column, the simple fact is: viruses constantly change. 

 

We’ve already seen multiple strains, new clades, and additional reassortants (H5N2, H5N3, H5N1) emerge since the H5N8 virus first appeared in early 2014, and more are undoubtedly on the horizon.  How they will behave, and the threat they pose to humans, may change as well. 

For now,  the news remains good, at least in so far as human infection is concerned. 

 

For the poultry industry, however, there is considerably less to celebrate. 

 

H5N8 and it’s reassortant H5N2 progeny appear to spread faster, and more easily by wild and migratory birds than any HPAI virus previously observed.  It is highly pathogenic in chickens, turkeys, and ducks - and if Taiwan’s outbreak is any indication (875 farms & counting) - once it enters a region’s poultry population, it is capable of spreading with alarming speed. 

All of which means that H5N8 (and its descendents) have staying power, and are likely to be with us for some time.

Research: Ferret H5N1 Infection Via Consumption Of Infected Chicken

Photo Credit Wikipedia

 

 

# 8704

 

Although we’ve seen numerous warnings from public health agencies about the dangers of consuming undercooked poultry products in those areas of Asia and the Middle East where H5N1 is endemic, most of the evidence for that risk has been anecdotal.   We’ve seen a relatively small number of human H5N1 infections where consumption of undercooked poultry, or raw duck blood pudding, was been strongly suspected as the route of infection. 

 

Poultry and eggs are considered safe if handled and cooked properly.  Consumption of raw blood pudding (duck or pig), a delicacy in Asia, is probably never a good idea as it carries other additional risks, including Strep Suis infection (see A Streptococcus suis Round Up).

.

 

In 2010, we saw a study (see H5N1 Can Replicate In Human Gut) that provided additional evidence that the bird flu virus can thrive in the human gastrointestinal system. Researchers found that Avian Influenza A(H5N1) Viruses Can Directly Infect and Replicate in Human Gut Tissues.

 

We’ve also seen numerous reports over the years of cats infected with the H5N1 virus after consuming infected birds.  The following comes from a World Health Organization GAR report from 2006.

H5N1 avian influenza in domestic cats

28 February 2006

(EXCERPTS)

Several published studies have demonstrated H5N1 infection in large cats kept in captivity. In December 2003, two tigers and two leopards, fed on fresh chicken carcasses, died unexpectedly at a zoo in Thailand. Subsequent investigation identified H5N1 in tissue samples.

In February 2004, the virus was detected in a clouded leopard that died at a zoo near Bangkok. A white tiger died from infection with the virus at the same zoo in March 2004.

In October 2004, captive tigers fed on fresh chicken carcasses began dying in large numbers at a zoo in Thailand. Altogether 147 tigers out of 441 died of infection or were euthanized. Subsequent investigation determined that at least some tiger-to-tiger transmission of the virus occurred.

 

In 2006, Dr. C.A. Nidom demonstrated that of 500 cats he tested in and around Jakarta, 20% had antibodies for the bird flu virus.  And in 2007 the FAO warned that: Avian influenza in cats should be closely monitored, although so far no sustained virus transmission in cats or from cats to humans has been observed.

 

Dogs are not exempt, as in 2006 the EID Journal published a Dispatch Fatal Avian Influenza A H5N1 in a Dog that documented a a fatal outcome following ingestion of an H5N1-infected duck in Thailand in 2004.

 

In 2011 we looked at a study that examined Gastrointestinal Bird Flu Infection In Cats, and as recently as 2012 the OIE reported on Cats Infected With H5N1 in Israel.

 

All of which brings us to a new short report that appears in Veterinary Research, that attempts to quantify the viral dose needed to infect ferrets through ingestion of infected meat.   First the link and abstract (the entire study is available), and an excerpt from the Discussion, then I’ll be back with a little more.

 

High doses of highly pathogenic avian influenza virus in chicken meat are required to infect ferrets

Kateri Bertran and David E Swayne

Author Affiliations

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Veterinary Research 2014, 45:60  doi:10.1186/1297-9716-45-60

Published: 3 June 2014

Abstract (provisional)

High pathogenicity avian influenza viruses (HPAIV) have caused fatal infections in mammals through consumption of infected bird carcasses or meat, but scarce information exists on the dose of virus required and the diversity of HPAIV subtypes involved. Ferrets were exposed to different HPAIV (H5 and H7 subtypes) through consumption of infected chicken meat.

The dose of virus needed to infect ferrets through consumption was much higher than via respiratory exposure and varied with the virus strain. In addition, H5N1 HPAIV produced higher titers in the meat of infected chickens and more easily infected ferrets than the H7N3 or H7N7 HPAIV.

The complete article is available as a provisional PDF. The fully formatted PDF and HTML versions are in production.

Discussion

In  conclusion,  relatively  high  concentrations  of  H5N1  HPAIV  are  required  to  produce infection  and  death  by  consumption  of  infected  meat  in  ferrets  as  compared  to  respiratory exposure.  Ingestion  of  HPAIV-infected  meat  can  produce  infection  that  primarily  involves  the respiratory tract but can also spread systemically depending on both the virus strain and virus dose received. Although human infections by HPAIV through direct oral contact have  been occasionally reported [12,13], airborne virus or contact with fomites is still considered the main route of exposure in human species [1].

 

Essentially researchers used 9 ferrets per virus tested, dividing them into three groups; low dose, medium dose, and high dose. They then compared morbidity, and mortality, seroconversion rates, and finally necropsy and histopathology test results to determine which viruses were able to infect via the oral consumption route, their effects, and how much of a viral load was required.

 

H5N1 viruses tended to replicate to higher titers in poultry meat than did the H7 viruses tested, and therefore were more infectious. 

 

Interestingly (but not surprisingly), there was a good deal of variability in the ferret outcomes between the two HPAI H5N1 strains (Mong/05 & VN/04) tested. None of the Mong/05 infected ferrets died, and most showed little or no signs of illness. Seven of nine seroconverted. Two of the VN/04 infected ferrets died, while two other seroconverted.

 

As this study illustrates, different clades of the H5N1 virus often demonstrate different degrees of virulence, something we looked at back in 2012 in Differences In Virulence Between Closely Related H5N1 Strains.

 

With the caveat that it is always a bit perilous to transpose animal study results to humans, this study supports the notion that consumption of improperly cooked avian-flu-infected poultry products could be reasonably assumed to pose a health risk.  

 

The good news, at least for ferrets, is that it takes a fairly large helping, and  the `right’ strain of virus, to prove fatal.

Study: Airborne Transmission Of H7N1 in Ferrets After Serial Passage

Classic serial passage study, albeit with ducks instead of ferrets

 

# 8428

 

When novel flu viruses jump species, they rarely do so fully adapted to the new host. There is generally period of transition – which may be measured in days, weeks, years . . . or even decades -  before the virus can adapt to the new host species.

 

Sometimes the gulf between the original host and the new species is too great, and this adaptation never takes place.

 

Even though we don’t fully understand how it works, the concept is fairly simple.

 

When a flu virus infects a cell, it immediately sets upon making thousands of copies of itself.  But single-stranded RNA flu viruses are notoriously sloppy replicators, and some of these copies will invariably carry small transcription errors.   Most of these `variants’  will prove either neutral or detrimental to the survival and propagation of the virus, but occasionally a change will occur increases its biological fitness in the new host.

 

Those, as you might expect, are the ones that thrive and perpetuate themselves. 

 

Which is why we are always concerned whenever a novel flu virus jumps to humans, as each instance is another opportunity for the virus to `figure us out’.

 

One of the classic lab experiments used to `hurry’  this evolutionary process along is called a serial passage experiment (see graphic at top of this post), where an test subject (usually a mouse or ferret) is infected with a virus, and that virus is then collected and used to inoculate another test subject.  This process is repeated a number of times.

 

After 10 or so iterations, the virus is then examined for `adaptive changes’ and/or changes in behavior (ie. virulence, transmissibility).  Sometimes, after multiple passes through a series of hosts, the virus picks up mutations that favor its survival in the new species. 

 

This is essentially how Ron Fouchier created a `mammalian-adapted’ H5N1 virus in the laboratory in 2011, and it mimics what viruses do in the wild, albeit at an artificially enhanced speed.

 

For a flu virus to spark a pandemic, it basically needs to meet three criteria:

 

1. It needs to be able to infect humans
2. It needs to be pathogenic in humans (causes disease)
3. It needs to be efficiently transmitted from human-to-human

 

The avian influenza viruses we’ve been watching (H5N1, H7N9, H9N2, H7N7,  etc) all appear to meet the first two criteria (although severity of disease varies greatly between subtypes), but so far item #3 remains absent.

 

The primarily barrier to a pandemic appears to be a lack of `airborne transmission’  between humans.

 

Since ferrets are highly susceptible to influenza, and exhibit a similar respiratory response to infection to humans (coughing & sneezing), they are often used for transmissibility studies. 

 

Infected ferrets are placed in cages adjacent to healthy ferrets, but any direct contact is prevented.  If the healthy ferrets catch the virus, its a pretty good indication of airborne transmission.

 

Today, we’ve a study appearing in the Journal of Virology that takes the avian H7N1 virus – passes it serially through ferrets 10 times  – and then tests the virus for both transmissibility and virulence.  The end result was an H7N1 virus that was transmissible via the airborne route (in ferrets) with no apparent loss of virulence.

 

 

Airborne Transmission of Highly Pathogenic H7N1 Influenza in Ferrets

Troy C. Sutton1, Courtney Finch, Hongxia Shao, Matthew Angel, Hongjun Chen, Ilaria Capua, Giovanni Cattoli, Isabella Monne and Daniel R. Perez

Avian H7 influenza viruses are recognized as potential pandemic viruses as personnel often become infected during poultry outbreaks. H7 infections in humans typically cause mild conjunctivitis; however, the H7N9 outbreak in the spring of 2013 has resulted in severe respiratory disease. To date, no H7 viruses have acquired the ability for sustained transmission in humans.

Airborne transmission is considered a requirement for the emergence of pandemic influenza, and advanced knowledge of the molecular changes or signature required for transmission would allow early identification of pandemic vaccine seed stocks, screening and stockpiling of antiviral compounds, and focused eradication efforts on flocks harboring threatening viruses.

Thus, we sought to determine if a highly pathogenic influenza A H7N1 (A/H7N1) vrus, with no previous history of human infection, could become airborne transmissible in ferrets.

We show that after 10 serial passages, A/H7N1 developed the ability to transmit to co-housed and airborne contact ferrets. Four amino acid mutations (PB2 T81I, NP V284M, M1 R95K, and Q211K) in the internal genes and a minimal amino acid mutation (K/R313R) in the stalk region of the HA protein were associated with airborne transmission. Furthermore, transmission was not associated with a loss of virulence.

These findings highlight the importance of the internal genes in host adaptation and suggest that natural isolates carrying these mutations be further evaluated. Our results demonstrate that a highly pathogenic avian H7 virus can become airborne transmissible in a mammalian host, and support on-going surveillance and pandemic H7 vaccine development.

Importance: The major findings of this report are that a highly pathogenic strain of H7N1 avian influenza can be adapted to become airborne transmissible in mammals without mutations altering the receptor specificity. Changes in receptor specificity have been shown to play a role in the ability of avian influenza viruses to cross the species barrier and these changes are assumed to be essential. The work herein challenges this paradigm, at least for the influenza viruses of the H7 subtype, which have recently become the focus of major attention as they have crossed to humans.

 

 

A bit surprisingly, four of the five amino acid changes that were associated with airborne transmission were found to occur in the internal genes (PB2, NP, M1) of the virus. Given the history of H9N2 donating its internal genes to novel reassortants (see Study: Sequence & Phylogenetic Analysis Of Emerging H9N2 influenza Viruses In China), these findings may help identify potential surveillance targets in that subtype, and others. 

 

This isn’t the first time we’ve seen evidence of airborne transmission of an H7 virus in ferrets.

 

In 2013, in Nature: Limited Airborne Transmission Of H7N9 Between Ferrets & Science: H7N9 Transmissibility Study In Ferrets), we saw lab experiments that showed this H7 avian flu virus could be transmitted between ferrets (albeit at low levels) via respiratory droplets.

 

So far, while airborne transmission has been demonstrated (in ferrets) in the lab, we’ve yet to see evidence of sustained and efficient airborne transmission of these novel avian viruses in humans.

 

But nature’s lab is open 24/7, new reassortant flu viruses are appearing all the time, and just because it hasn’t happened yet doesn’t mean it can’t happen sometime in the future.

Nature: Limited Airborne Transmission Of H7N9 Between Ferrets

Photo Credit Wikipedia

 

# 7556

 

Yesterday’s report on Omani camels carrying antibodies to the MERS Coronavirus (see Lancet: Camels Found With Antibodies To MERS-CoV-Like Virus) pretty much dominated the headlines in the flu world, but another study deserving our attention appeared in the Journal Nature as well.

 

Researchers from the Erasmus Medical Center in the Netherlands University of Cambridge in the United Kingdom infected four ferrets with the Anhui/1/2013 strain of H7N9, and then placed  uninfected ferrets in cages next to them.

 

Three of the four unexposed ferrets became infected, demonstrating limited airborne transmission (efficiency estimated somewhere between that of seasonal flu and avian flu). Genetic sequencing showed the virus they carried to be identical to the original test virus.  

 

These researchers did find that after ferret passage, variants with preferential binding to avian (a2,3) receptor cells, higher pH of fusion, and lower thermostability were selected, which potentially could reduce ongoing transmissibility of the virus in mammals.

 

Overall, these findings are similar to other ferret transmissibility studies we’ve seen published over the summer (see Science: H7N9 Transmissibility Study In Ferrets).

 

The link to the Nature Abstract follows:

 

Limited airborne transmission of H7N9 influenza A virus between ferrets

Mathilde Richard, Eefje J. A. Schrauwen, Miranda de Graaf, Theo M. Bestebroer, Monique I. J. Spronken, Sander van Boheemen, Dennis de Meulder, Pascal Lexmond, Martin Linster, Sander Herfst, Derek J. Smith, Judith M. van den Brand, David F. Burke, Thijs Kuiken, Guus F. Rimmelzwaan, Albert D. M. E. Osterhaus & Ron A. M. Fouchier

ABSTRACT (Excerpt)

Here we show that although the A/Anhui/1/2013 A(H7N9) virus harbours determinants associated with human adaptation and transmissibility between mammals, its airborne transmissibility in ferrets is limited, and it is intermediate between that of typical human and avian influenza viruses. Multiple A(H7N9) virus genetic variants were transmitted.

Upon ferret passage, variants with higher avian receptor binding, higher pH of fusion, and lower thermostability were selected, potentially resulting in reduced transmissibility. This A(H7N9) virus outbreak highlights the need for increased understanding of the determinants of efficient airborne transmission of avian influenza viruses between mammals.

 

 

While laboratory experiments have consistently shown the H7N9 virus can transmit reasonably well from ferret-to-ferret via direct contact or respiratory droplet, thus far the Chinese have reported no signs of sustained human-to-human transmission in the field.

 

The reasons behind this disparity, and whether this apparent lack of transmissibility in humans will continue, are among the many questions on the list of researchers studying the virus.

Science: H7N9 Transmissibility Study In Ferrets

 

Photo Credit Wikipedia

 

UPDATED: CIDRAP NEWS now has an extensive review of this paper up on their website, with expert commentary provided by Dr. Ian MacKay. 

 

Study: H7N9 highly transmissible by airborne route

  Highly recommended.

 

 

 

# 7496

 

 

While the welcomed lull in avian influenza cases in Eastern China over the past six weeks has taken H7N9 largely out of the daily headlines, history has shown that avian flu viruses often go `quiet’ during the warm summer months, only to reappear again in the fall or winter.

 

Complicating matters, we still don’t know the source of this virus, or exactly how it managed to spread across tens of thousands of square kilometers of Eastern China - and infect at least 132 people - in a matter of a few weeks.

 

So over the summer researchers have continued to examine the H7N9 virus, trying to gauge its pandemic potential should it return with colder weather this fall.

 

Last week we saw two studies in the Journal Nature  (see Nature: H7N9 Pathogenesis and Transmissibility In Ferrets & Mice & CIDRAP NEWS  article New studies on H7N9 raise pandemic concerns) that suggested the H7N9 virus might be better equipped to spark a pandemic than previously thought.

 

Researchers determined that while the virus did not appear to transmit as easily as seasonal flu via respiratory droplets between ferrets, once acquired, the virus replicated at a much higher rate than one normally sees with seasonal flu.

 

Today, we’ve a complex and fascinating new study by scientists from Harbin Veterinary Research Institute and the Gansu Agricultural University appearing in the Journal Science that gives us a detailed look at two critical issues; the pathogenicity and transmissibility of the virus (in mice & ferrets). 

 

Ferrets – whose respiratory system (and susceptibility to flu) are reasonably close to that of humans – are often used in transmissibility and pathogenicity studies of influenza. 

 

Today’s study tested several different H7N9 isolates (acquired from birds, and from humans) for transmissibility, and even though their HA and NA proteins were genetically quite similar, at least one H7N9 isolate transmitted readily via respiratory droplets among ferrets.

 

The abstract (see below), only scratches the surface of research conducted in this study.

 

H7N9 Influenza Viruses Are Transmissible in Ferrets by Respiratory Droplet

Science DOI: 10.1126/science.1240532

Qianyi Zhang, Jianzhong Shi, Guohua Deng, Jing Guo, Xianying Zeng, Xijun He, Huihui Kong, Chunyang Gu,  Xuyong Li, Jinxiong Liu, Guojun Wang, Yan Chen,  Liling Liu,  Libin Liang, Yuanyuan Li, Jun Fan, Jinliang Wang,  Wenhui Li, Lizheng Guan,  Qimeng Li, Huanliang Yang,  Pucheng Chen,  Li Jiang,Yuntao Guan, Xiaoguang Xin, Yongping Jiang, Guobin Tian, Xiurong Wang, Chuanling Qiao, Chengjun Li,  Zhigao Bu, Hualan Chen

Abstract (EXCERPT)

We systematically analyzed H7N9 viruses isolated from birds and humans. The viruses were genetically closely related and bound to human airway receptors; some also maintained the ability to bind to avian airway receptors. The viruses isolated from birds were nonpathogenic in chickens, ducks, and mice; however, the viruses isolated from humans caused up to 30% body weight loss in mice.

 

Most importantly, one virus isolated from humans was highly transmissible in ferrets by respiratory droplets. Our findings indicate nothing to reduce the concern that these viruses can transmit between humans.

 

 

While I’m sure CIDRAP NEWS will have a more detailed look later today (I’ll post a link), a few of the high points in this study include:

 

• Researchers tested more than 10,700 samples taken from poultry farms, live market birds, wild bird habitats, and even poultry and swine slaughter houses and only managed to find 52 samples that were H7N9 positive (all but 2 were found in live-markets)
• Chickens intravenously inoculated with two early strains of the virus showed no signs of illness indicating the H7N9 is largely non-pathogenic in chickens
• Isolates taken from humans appeared to be more pathogenic in ferrets and mice than those taken from birds, suggesting adaptation of the virus may occur after the virus jumps to humans.
• All of the human isolates had either the 627K or 701N amino acid changes in their PB2 (both associated with increased virulence and transmission in mammals) - while the avian isolates did not - again suggesting that adaptive mutations may have occurred during replication of the virus in the human host.
• Mice inoculated with avian H7N9 isolates showed no signs of disease signs or deaths.
• Mice inoculated with human derived H7N9 isolates experienced significant weight loss & pathogenesis.
• In ferret transmissibility studies, four of the five viruses tested could be transmitted between ferrets in direct contact with each other, and one transmitted with high efficiency via respiratory droplets.

 

Being non-pathogenic in chickens, this virus has the potential to spread stealthily, and its rapid spread across multiple provinces in China suggests it transmits efficiently among poultry species.

 

This research suggests that the H7N9 virus already binds pretty well to human-like (a2,6) receptor cells, and it replicates efficiently in a mammalian (ferret) host.

 

Additionally, the H7N9 virus appears capable of accruing adaptive mutations that enhance both its virulence and transmissibility once it starts to replicate within a human host.

 

And perhaps most worrisome of all, at least one isolate tested already demonstrates the ability to transmit readily via respiratory droplets in ferrets.

 

Complicating matters, earlier this week we saw a study (see mBio: Antiviral Resistance In H7N9) suggesting that antiviral resistance may form quickly in patients infected with the H7N9 virus.

 

All qualities that could help make the H7N9 virus a formidable foe should we see it return in the fall.

Branswell: Studies Show Transmissibility Of H7N9 In Ferrets

Credit NIAID

 

# 7314

 

Helen Branswell has the details today on a new study which appears in the Journal Science, that looks at the ability of the avian H7N9 virus – recently emerged in China – to infect and transmit among ferrets.

 

Ferrets are considered a reasonable mammalian substitute for humans when testing respiratory viruses because their lung physiology is similar, and because they cough and sneeze when infected, very much as humans do.

 

As Helen reports, researchers found signs that the H7N9 virus has already made adaptations to mammalian hosts not normally seen in `wild’ avian flu viruses, and as such, must be considered `a serious threat’.

 

First, I’d invite you to follow the link to read Helen’s article, then I’ll return with more.

 

H7N9 bird flu virus spreads among mammals, inches closer to human-to-human transmission, experts warn

Helen Branswell, Canadian Press | 13/05/23 2:50 PM ET

TORONTO — A new study shows that the H7N9 flu virus can pass between ferrets, even sometimes spreading by airborne transmission.

 

While the airborne spread wasn’t highly efficient, the work suggests this virus is more closely adapted to spread among mammals than other bird flu viruses.

(Continue . . .)

 

The study can be found at:

 

Published Online May 23 2013
Science DOI: 10.1126/science.1239844

Infectivity, Transmission, and Pathology of Human H7N9 Influenza in Ferrets and Pigs

H. Zhu, D. Wang, D. J. Kelvin, L. Li, Z. Zheng, S.-W. Yoon, S.-S. Wong, A. Farooqui, J. Wang, D. Banner, R. Chen, R. Zheng, J. Zhou, Y. Zhang, W. Hong, W. Dong, Q. Cai, M. H. A. Roehrl, S. S. H. Huang, A. A. Kelvin, T. Yao, B. Zhou, X. Chen, G. M. Leung, L. L. M. Poon, R. G. Webster, R. J. Webby, J. S. M. Peiris, Y. Guan,Y. Shu

The emergence of the H7N9 influenza virus in humans in Eastern China has raised concerns that a new influenza pandemic could occur. Here, we used a ferret model to evaluate the infectivity and transmissibility of A/Shanghai/2/2013 (SH2), a human H7N9 virus isolate. This virus replicated in the upper and lower respiratory tracts of the ferrets and was shed at high titers for 6 to 7 days, with ferrets showing relatively mild clinical signs.

SH2 was efficiently transmitted via direct contact, but less efficiently by airborne exposure. Pigs could be productively infected by SH2 and shed virus for 6 days but were unable to transmit the virus to other animals. Under appropriate conditions human-to-human transmission of the H7N9 virus may be possible.

 

Today the NIH published a press release on this study, portions of which I’ve excerpted below:

 

Ferrets, Pigs Susceptible to H7N9 Avian Influenza Virus

NIH-Funded Study Examined Transmissibility of Emerging Virus

WHAT:
Chinese and U.S. scientists have used virus isolated from a person who died from H7N9 avian influenza infection to determine whether the virus could infect and be transmitted between ferrets. Ferrets are often used as a mammalian model in influenza research, and efficient transmission of influenza virus between ferrets can provide clues as to how well the same process might occur in people. The research was supported, in part, by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

 

The researchers dropped H7N9 virus into the noses of six ferrets. A day later, three uninfected ferrets were placed inside cages with the infected animals, and another three uninfected ferrets were placed in cages nearby. All the uninfected ferrets inside the cages became infected, while only one of three placed in nearby cages became infected. The team concluded that the virus can infect ferrets and be transmitted between ferrets both by direct contact and, less efficiently, by air. The scientists detected viral material in the nasal secretions of the ferrets at least one day before clinical signs of disease became apparent. The potential public health implication of this observation is that a person infected by H7N9 avian influenza virus who does not show symptoms could nevertheless spread the virus to others.

 

The researchers also infected pigs with the human-derived H7N9 virus. In natural settings, pigs can act as a virtual mixing bowl to combine avian- and mammalian-specific influenza strains, potentially allowing avian strains to better adapt to humans. New strains arising from such mixing have the potential to infect humans and spark a pandemic, so information about swine susceptibility to H7N9 could help scientists gauge the pandemic potential of the avian virus. Unlike the ferrets, infected pigs in this small study did not transmit virus to uninfected pigs, either through direct contact or by air. All the infected ferrets and pigs showed mild signs of illness, such as sneezing, nasal discharge, and lethargy, but none of the infected animals became seriously ill.

ARTICLE:
H Zhu et al. Infectivity, transmission and pathogenesis of human-isolated H7N9 influenza virus in ferrets and pigs. Science DOI: 10.1126/science.1239844 (2013).