mBio: A Novel Pathogenic Mammalian Orthoreovirus In Diarrheic American Pigs

Photo Credit CDC EID Journal

 

# 10,064

 

While American poultry farmers are gearing up to battle HPAI, for the past two years North American swine farmers have been dealing with several recently discovered novel coronaviruses causing diarrheal disease, and often death, in young piglets. 

 

• We took our first detailed look at this outbreak in October of 2013, in mBio: PEDV - Porcine Epidemic Diarrhea Virus - An Emerging Coronavirus.  While distantly related to SARS and MERS (both are betacoronaviruses),  PEDV is an alphacoronavirus.
• In early 2014, the Ohio Department of Agriculture officially announced that a never-before-seen porcine deltacoronavirus (PDCoV) had been identified in the United States (see New, non-PED Coronavirus detected in pigs with diarrhea).
• With a plethora of porcine pathogens to deal with , the USDA  lumped them together last summer into the general category of SECD – or Swine Enteric Coronavirus Diseases.  

 

We’ve seen no evidence of human infection due to these swine coronaviruses, so they are not currently considered a zoonotic disease.  Which is not to say that one or both couldn’t someday pose a threat. Coronaviruses – like all RNA viruses – tend to evolve and mutate at a fairly rapid rate (see discussion of new zoonotic coronaviruses).

Porcine epidemic diarrhea has now been reported in 32 states, and unexpectedly has hit some of the same herds more than once, leading researchers to wonder if there might be more pathogens at work than are already identified.  

 

All of which leads us to a fascinating bit of viral detective work, where researchers have isolated and identified yet another pathogenic diarrhea-inducing virus circulating in American pigs. 

 

This time, however, the culprit is not a coronavirus – but a novel mammalian orthoreovirus (MRV).

 

First the abstract from a much larger (open access) mBio research article, after which I’ll return with more:

A Novel Pathogenic Mammalian Orthoreovirus from Diarrheic Pigs and Swine Blood Meal in the United States

Athmaram Thimmasandra Narayanappa^a, Harini Sooryanarain^a,  Jagadeeswaran Deventhiran^a, Dianjun Cao^a, Backiyalakshmi Ammayappan Venkatachalam^a,  Devaiah Kambiranda^b,  Tanya LeRoith^a,  Connie Lynn Heffron^a,  Nicole Lindstrom^a,  Karen Hall^a,  Peter Jobst^a,  Cary Sexton^c,  Xiang-Jin Meng^a, Subbiah Elankumaran^a 

ABSTRACT

Since May 2013, outbreaks of porcine epidemic diarrhea have devastated the U.S. swine industry, causing immense economic losses. Two different swine enteric coronaviruses (porcine epidemic diarrhea virus and Delta coronavirus) have been isolated from the affected swine population. The disease has been reported from at least 32 states of the United States and other countries, including Mexico, Peru, Dominican Republic, Canada, Columbia, Ecuador, and Ukraine, with repeated outbreaks in previously infected herds.

Here we report the isolation and characterization of a novel mammalian orthoreovirus 3 (MRV3) from diarrheic feces of piglets from these outbreaks in three states and ring-dried swine blood meal from multiple sources. MRV3 could not be isolated from healthy or pigs that had recovered from epidemic diarrhea from four states. Several MRV3 isolates were obtained from chloroform-extracted pig feces or blood meal in cell cultures or developing chicken embryos.

Biological characterization of two representative isolates revealed trypsin resistance and thermostability at 90°C. NextGen sequencing of ultrapurified viruses indicated a strong homology of the S1 segment to mammalian and bat MRV3. Neonatal piglets experimentally infected with these viruses or a chloroform extract of swine blood meal developed severe diarrhea and acute gastroenteritis with 100% mortality within 3 days postinfection. Therefore, the novel porcine MRV3 may contribute to enteric disease along with other swine enteric viruses. The role of MRV3 in the current outbreaks of porcine epidemic diarrhea in the United States remains to be determined, but the pathogenic nature of the virus warrants further investigations on its epidemiology and prevalence.

 

This paper goes on to succinctly describe MRV viruses as:

 

The family Reoviridae comprises 15 genera of double-stranded RNA (dsRNA) viruses (9). Orthoreoviruses with 10 discrete RNA segments have been isolated from a wide variety of animal species, including bats, civet cats, birds, reptiles, pigs, and humans (10, 11).

Most orthoreoviruses are recognized to cause respiratory infections, gastroenteritis, hepatitis, myocarditis, and central nervous system disease in humans, animals, and birds (11); orthoreovirus genomes are prone to genetic reassortment and intragenic rearrangement (11, 12). The exchange of RNA segments between viruses could lead to molecular diversity and evolution of viruses with increased virulence and host range (13, 14).

MRV serotypes 1 to 3 were associated with enteritis, pneumonia, or encephalitis in swine around the world, including China and South Korea (15– 18). The zoonotic potential of MRV3 has been reported recently (19–21). However, porcine orthoreovirus infection of pigs was unknown previously in the United States.

 

The entire study is highly detailed, and well worth reading in its entirety.

 

In recent years we’ve seen increased interest and research into orthoreoviruses, with an particular eye towards their ability to reassort and to perhaps someday pose a greater threat to human health.

 

In 2007 we saw  the emergence of what is now called the Melaka Virus (see First Bird Flu, Now Bat Flu & Why You Should Catch `Contagion’) – an orthoreovirus carried by bats in Malaysia.

 

Since then, several additional bat-borne orthoreoviruses have been identified, including the Xi-River, Kampar, Sikamat, HK23629/07 and Broome virus.  As bats are the most abundant and geographically dispersed vertebrates on earth, their ability to carry and vector dangerous diseases without ill-effect (i.e. Rabies, Nipah, Hendra, even influenza) is increasingly a topic of study.

Just last week, PLoS One published a study looking at a potential reassortment of bat, pig, and/or human MRV strains in a bat reservoir in China.

 

Isolation and Identification of a Natural Reassortant Mammalian Orthoreovirus from Least Horseshoe Bat in China

Lihua Wang,^1,2 Shihong Fu,^1,2 Lei Cao,^1,2 Wenwen Lei,^1,2 Yuxi Cao,^1,2 Jingdong Song,^1,2 Qing Tang,^1,2 Hailin Zhang,³ Yun Feng,³ Weihong Yang,³ and Guodong Liang^1,2,*

Abstract

Background

Mammalian orthoreoviruses (MRVs) have a wide geographic distribution and can infect virtually all mammals. Infections in humans may be either symptomatic or asymptomatic. This study describes the isolation and identification of a natural reassortant MRV from least horseshoe bats (Rhinolophus pusillu) in China, referred to as RpMRV-YN2012.

<SNIP>

MRV infection in humans has been shown to be fairly common and the infections are often shown to be asymptomatic or associated with mild, self-limiting respiratory or gastrointestinal illness in infants and children [3]. Recent studies have shown that MRV can cause severe illnesses in humans and other mammals, including upper respiratory tract infections, encephalitis, and diarrhea[4, 5, 18].

(Continue . . . )

And a couple of years ago, in the Journal of Virology, we saw:

 

High Similarity of Novel Orthoreovirus Detected in a Child Hospitalized with Acute Gastroenteritis to Mammalian Orthoreoviruses Found in Bats in Europe

Andrej Steyer^a, Ion Gutiérrez-Aguire^b,^e, Marko Kolenc^a, Simon Koren^c, Denis Kutnjak^b, Marko Pokorn^d, Mateja Poljšak-Prijatelj^a, Nejc Rački^b, Maja Ravnikar^b,^e, Martin Sagadin^a, Adela Fratnik Steyer^a and Nataša Toplak^c 

ABSTRACT

Mammalian orthoreoviruses (MRVs) are known to cause mild enteric and respiratory infections in humans. They are widespread and infect a broad spectrum of mammals. We report here the first case of an MRV detected in a child with acute gastroenteritis, which showed the highest similarity to an MRV reported recently in European bats.

(Continue . . . )

 

None of which is to suggest that MRVs are destined to be the next big public health threat, or that the MRV3 virus described in the mBio paper today poses any immediate threat to human health.

 

But they do serve as a reminder that the constellation of  viruses out there with zoonotic potential is much greater and more widespread than we know, and that these viruses are not static - but are instead moving targets – evolving, reassorting, and spreading geographically at truly impressive rates.

 

We’ll return to today’s mBio study to close, with the author’s summation of the importance of their findings:

 

IMPORTANCE Porcine orthoreoviruses causing diarrhea have been reported in China and Korea but not in the United States. We have isolated and characterized two pathogenic reassortant MRV3 isolates from swine fecal samples from porcine epidemic diarrhea outbreaks and ring-dried swine blood meal in the United States. These fecal and blood meal isolates or a chloroform extract of blood meal induced severe diarrhea and mortality in experimentally infected neonatal pigs. Genetic and phylogenetic analyses of two MRV3 isolates revealed that they are identical but differed significantly from nonpathogenic mammalian orthoreoviruses circulating in the United States. The present study provides a platform for immediate development of suitable vaccines and diagnostics to prevent and control porcine orthoreovirus diarrhea.

Fair Biosecurity & H3N2 In North Dakota Show Pigs

 

# 8901

 

County and State Fair season is underway in the northern states and will continue across the nation well into fall. One of the highlights for many visitors are the agricultural exhibits, including livestock exhibitions.  While educational, entertaining, and financially lucrative, there are admittedly some downsides.

Bringing together animals from farms all over the region provides unique opportunities to swap pathogens amongst themselves, and potentially spread them to handlers and the public.

 

In years past, the concern has centered primarily on swine flu, but the recent emergence of two new swine coronaviruses – PEDV & PDCoV  (see SECD: Another Emerging Coronavirus Threat) have complicated matters as well.  Unlike the swine influenzas, however, SECDs - or Swine Enteric Coronavirus Diseases – are not known to transmit to humans.

 

While they generally cause mild symptoms in adult pigs, among piglets, the mortality rate can run close to 100%. 

 

In some regions, fair administrators have implemented a terminal show policy – where pigs exhibited at the fair must be sent to market at the show’s end, rather than back home (or worse, to another fair) to prevent the potential spread of porcine diseases. 

 

This report (and video) from a local Wisconsin TV station.

Terminal show policy in place to control swine virus

The PED virus has had a significant impact on pig populations in the United States in the last two years

Author: Dave Delozier, ddelozier@wisctv.com

Published On: Jul 25 2014 05:44:58 PM CDT

PORTAGE, Wis. -

While most pig exhibitors attend county fairs with the expectation their animal will be sold to market, it is now becoming a certainty.  Because of concerns about the spread of a deadly virus, Porcine Epidemic Diarrhea or PED, county fairs have adopted a terminal show policy.  That means a pig shown at a county fair must be sold to market at the shows end and cannot be taken back to a farm.

(Continue . . . )

 

Beyond the opportunities for porcine diseases to spread between pigs, fairs also provide lots of human-animal contact, which can lead to the spread of infections from humans-to-pigs, and from pigs-to-humans. 

 

Illustrating the two-way nature of disease sharing - shortly after the 2009 H1N1 virus emerged in the human population - it began showing up in pig herds around the world (see Study: Reassortants of H1N1pdm & Swine H1 & H3 Viruses in Japan)

 

With the emergence of several swine variant influenza viruses in the past few years (H1N1v, H1N2v, H3N2v) – all able to jump to humans (albeit, not able to transmit efficiently) -  we are seeing a greater emphasis on fair biosecurity than ever before (see CDC: Measures to Minimize Influenza Transmission at Swine Exhibitions, 2014).

. 

Last week, in EID Journal: H3N2v Swine To Human Transmission At Agricultural Fairs – 2012, we looked at what was the most active year for swine variant transmission to humans, where the authors cautioned:

 

Swine-to-human transmission and human-to-swine transmission of influenza A virus are known to occur at fairs (28), highlighting the fact that swine in this setting are potentially exposed to multiple lineages of influenza A viruses simultaneously, making fairs ideal locations for genomic reassortment and novel virus formation.

 

Swine are highly susceptible to a variety of flu viruses (human, swine, avian) - and are viewed as excellent `mixing vessels’, allowing viruses to reassort into new hybrid strains.  This is how the 2009 H1N1 pandemic virus was created, after bouncing around swine herds for a decade or more.

 

State & local  fairs have instituted inspections for any signs of illness in livestock – but as we’ve discussed previously (see Asymptomatic Pigs: Revisited) - pigs can sometimes carry these viruses without showing any outward signs of infection.

 

While we’ve not seen any reports of human infection with swine variant influenza this summer, fair officials and health departments are understandably on heightened alert, and are taking steps to try to prevent that from happening.  All of which serves as prelude to this announcement (yesterday) by North Dakota’s Department of Health.

 

Influenza A H3N2 Variant Viruses (H3N2v)

Influenza A H3N2v is a non-human influenza virus that normally circulates in pigs. In 2011, a small number of humans were found to be infected with this virus. From 2011 to 2013, a total of 340 cases of H3N2v was identified in 13 states, resulting in 17 hospitalizations and one death. Most of these cases occured in the summer months, and most reported contact with pigs. Symptoms and severity of H3N2v infections in humans resemble that of seasonal influenza, and include fever, cough, sore throat, body aches, and headache. No cases have been identified at this time for 2014, and no cases in North Dakota have ever been reported.

On July 31, 2014 it was reported that three pigs at the 2014 North Dakota State Fair had been removed for illness and had tested positive for an H3N2 virus. The North Dakota Department of Agriculture put out the following news release:

North Dakota Department of Agriculture
July 31, 2014

For immediate release

Precautions advised regarding influenza

BISMARCK – The North Dakota Department of Agriculture (NDDA) and North Dakota Department of Health (NDDoH) received results from the National Veterinary Services Laboratory confirming that three pigs exhibited at the state fair in Minot have tested positive for an influenza A H3N2 virus strain. Although influenza can be passed from swine to people, there is no evidence at this time that any people have become ill as a result of exposure to these pigs.

 
NDDA animal health division staff inspects all animals displayed at the North Dakota State Fair. The pigs appeared healthy when they arrived at the fair and became ill thereafter. After being tested, they were removed from the fairgrounds by their owners at the recommendation of veterinarians. This is the first time that an influenza virus has been confirmed in swine at a fair in North Dakota.

“Fairs and exhibits are an excellent way to showcase livestock and expose the public to animal agriculture production,” said Agriculture Commissioner Doug Goehring. “When appropriate precautions are taken, there is minimal risk of spreading disease to the public.”

 
However, some influenza viruses can spread from pigs to people and from people to pigs. Spread from infected pigs to humans is thought to happen in the same way that seasonal influenza viruses spread between people; mainly through infected respiratory droplets created when an infected pig coughs. Swine influenza has not been shown to be transmissible to people through eating properly handled and prepared pork or other products derived from pigs.

According to the NDDoH, appropriate precautions to prevent the spread of influenza from pigs to people include the same types of measures used to prevent the spread of influenza between people; frequent hand washing and avoiding contact with those that are ill. Other precautions include not eating or drinking around animals and avoiding contact with material, such as bedding material, which has been in contact with pigs. Any exhibitor or visitor at high risk of serious flu complications, who is planning to attend a fair where pigs will be present, should consider avoiding pigs and swine barns. The NDDoH also encourages those who work with pigs to take precautions to avoid the spread of illness. Use masks and gloves when you work with ill animals to protect yourself against transfer of the virus.

“Washing hands prior to working with or handling animals and likewise after working with animals is a good practice,” State Veterinarian, Dr. Susan Keller said. “Swine producers should contact their veterinarians if they have any questions about influenza-like illnesses in their pigs. Vaccines are available that may prevent illness.”

According to the NDDoH, if you experience symptoms of influenza (fever, cough, sore throat, body aches, headache) after contact with animals, report that contact to your primary health care provider. Conversely, if you have influenza, avoid contact with pigs during your illness and for another week after symptoms have disappeared.

For more information about influenza, including the H3N2v flu, visit the health department’s influenza website at www.ndflu.com or call the North Dakota Department of Health at 701-328-2378. For recommendations for swine producers, visit the NDDA website at www.nd.gov/ndda/disease/h3n2-influenza or call the State Veterinarian’s office at 701-328-2655.

 

 

Although only 19 swine variant flu infections were reported last year,  in 2012 more that 300 cases were reported, with nearly all linked to fairgoers, mostly in Indiana & Ohio.  Given the limits of surveillance, and the likelihood that some number of mild or asymptomatic cases went undetected, both numbers probably under represent the true incidence of the disease.

Nevertheless, these swine variant viruses do no yet appear ready for prime time, as they have yet to show signs of sustained and efficient transmission in the community.  

 

They do, however, bear watching as research has shown only limited community immunity to these variant strains (see CIDRAP: Children & Middle-Aged Most Susceptible To H3N2v).

mBio: PEDV - Porcine Epidemic Diarrhea Virus – An Emerging Coronavirus

Photo Credit CDC EID Journal

 

# 7864

 

Over the past several months a newly emerging coronavirus – PEDV – has been identified in the United States, affecting swine herds in  at least 17 states, resulting in high mortality, particularly in piglets. The virus was first identified in the United States in May of this year, but there have been reports of the virus both in Asia and in Europe, going back several decades.

The University of Minnesota’s Center for Animal Health and Food Safety describes the virus thusly:

 

With the recent emergence of another coronavirus – MERS-CoV – and the history of human epidemic sparked by the SARS coronavirus a decade ago, there is understandable interest in PEDV both by agricultural and public health interests. 

 

It should be quickly noted, however, that we’ve seen no evidence of human infection due to PEDV coronavirus, so PEDV is not considered a zoonotic disease.

 

While SARS and MERS are both betacoronaviruses,  PEDV is an alphacoronavirus (two other genera also exist, Gammacoronavirus, and Deltacoronavirus).  The first two (alpha & beta) are believed to originate in bats (but are found in many other species), with the second two (Gamma & Delta) are believed to have an avian origin.

 

Although PED (porcine epidemic diarrhea) has been recognized in Asia since the 1970s, it has been considered exotic in North America.  Starting around 2010, China reported a sudden increase related pig deaths, which was the subject of the following CDC’s EID Journal dispatch published in August of 2012.

New Variants of Porcine Epidemic Diarrhea Virus, China, 2011

Wentao Li, Heng Li, Yunbo Liu, Yongfei Pan, Feng Deng, Yanhua Song, Xibiao Tang, and Qigai He

Abstract

In 2011, porcine epidemic diarrhea virus (PEDV) infection rates rose substantially in vaccinated swine herds. To determine the distribution profile of PEDV outbreak strains, we sequenced the full-length spike gene from samples from 9 farms where animals exhibited severe diarrhea and mortality rates were high. Three new PEDV variants were identified.

<SNIP>

The first confirmed PED case in the People’s Republic of China was reported in 1973. Almost 2 decades later, an oil emulsion, inactivated vaccine was developed and has since been in wide use throughout the swine industry in China. Until 2010, the prevalence of PEDV infection was relatively low with only sporadic outbreaks; however, starting in late 2010, a remarkable increase in PED outbreaks occurred in the pig-producing provinces.

(Continue . . . )

 

All of which serves as prelude to a study, published yesterday in the open access journal mBio, that takes a detailed look at the:

 

Origin, Evolution, and Genotyping of Emergent Porcine Epidemic Diarrhea Virus Strains in the United States

Yao-Wei Huang^a,b, Allan W. Dickerman^c, Pablo Piñeyro^a, Long Li^d, Li Fang^d, Ross Kiehne^e, Tanja Opriessnig^f,g, Xiang-Jin Meng^a

ABSTRACT

Coronaviruses are known to infect humans and other animals and cause respiratory and gastrointestinal diseases. Here we report the emergence of porcine epidemic diarrhea virus (PEDV) in the United States and determination of its origin, evolution, and genotypes based on temporal and geographical evidence. Histological lesions in small intestine sections of affected pigs and the complete genomic sequences of three emergent strains of PEDV isolated from outbreaks in Minnesota and Iowa were characterized. Genetic and phylogenetic analyses of the three U.S. strains revealed a close relationship with Chinese PEDV strains and their likely Chinese origin. The U.S. PEDV strains underwent evolutionary divergence, which can be classified into two sublineages. The three emergent U.S. strains are most closely related to a strain isolated in 2012 from Anhui Province in China, which might be the result of multiple recombination events between different genetic lineages or sublineages of PEDV. Molecular clock analysis of the divergent time based on the complete genomic sequences is consistent with the actual time difference, approximately 2 to 3 years, of the PED outbreaks between China (December 2010) and the United States (May 2013).

The finding that the emergent U.S. PEDV strains share unique genetic features at the 5′-untranslated region with a bat coronavirus provided further support of the evolutionary origin of PEDV from bats and potential cross-species transmission. The data from this study have important implications for understanding the ongoing PEDV outbreaks in the United States and will guide future efforts to develop effective preventive and control measures against PEDV.

IMPORTANCE The sudden emergence of porcine epidemic diarrhea virus (PEDV), a coronavirus, for the first time in the United States causes significant economic and public health concerns. Since its recognition in May 2013, PEDV has rapidly spread across the United States, resulting in high mortality in piglets in more than 17 States now.

The ongoing outbreaks of Middle East respiratory syndrome coronavirus in humans from countries in or near the Arabian Peninsula and the historical deadly nature of the 2002 outbreaks of severe acute respiratory syndrome coronavirus create further anxiety over the emergence of PEDV in the United States due to the lack of scientific information about the origin and evolution of this emerging coronavirus.

Here we report the detailed genetic characterization, origin, and evolution of emergent PEDV strains in the United States. The results provide much needed information to devise effective preventive and control strategies against PEDV in the United States.

<SNIP>

In summary, we report here the emergence of PEDV in the United States and detailed genetic and phylogenetic analyses of the complete genomic sequences of three emergent U.S. PEDV strains from Minnesota and Iowa. The findings that the emergent U.S. PEDV strains are most closely related to Chinese G2a strains suggest that the emergence of the PEDV in the United States likely originated from China. However, the exact source of the origin is difficult to identify at this point. The finding that the emergent PEDV strains in the United States share unique genetic features with a bat coronavirus further suggests a possible evolutionary origin of PEDV from bat species and potential cross-species transmission. The information presented in this study will guide the current control measures to stop the ongoing spread of PEDV in the United States and also provides important clues for the development of an effective vaccine against the emergent PEDV strains.

(Continue . . . )

Whether the result of an introduction from China, or evolutionary events here in the United States, pig producers are now confronted with at least three new variants of this virus.  PEVD has the potential to cause extensive economic damage to pork producers across the nation.

It is just one of the many coronaviruses that affect animals species, but thankfully, not humans. 

 

Other non-zoonotic coronaviruses include Infectious bronchitis virus (IBV) in birds, (TEGV) transmissible gastroenteritis in swine, Bovine coronavirus (BCV), Feline coronavirus (FCoV), canine coronavirus (CCoV), and coronaviruses that target turkeys and ferrets.

 

The rub, as always, is that viruses are moving targets.  As we’ve just seen, a number of new variants have appeared here in the United States and in China over the past three years.  None have shown any signs of infecting humans, but until 2012, we’d never seen evidence of the MERS-CoV jumping species either. 

 

Which illustrates the importance of good surveillance and testing of livestock for infectious diseases, even those that don’t currently pose a threat to human health.

 

Because with viruses, an unexpected change in behavior can be literally only a few mutations away.