Tuesday, May 19, 2015

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’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 Narayanappaa, Harini Sooryanaraina,  Jagadeeswaran Deventhirana, Dianjun Caoa, Backiyalakshmi Ammayappan Venkatachalama,  Devaiah Kambirandab,  Tanya LeRoitha,  Connie Lynn Heffrona,  Nicole Lindstroma,  Karen Halla,  Peter Jobsta,  Cary Sextonc,  Xiang-Jin Menga, Subbiah Elankumarana 


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 Liang1,2,*



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.


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 Steyera, Ion Gutiérrez-Aguireb,e, Marko Kolenca, Simon Korenc, Denis Kutnjakb, Marko Pokornd, Mateja Poljšak-Prijatelja, Nejc Račkib, Maja Ravnikarb,e, Martin Sagadina, Adela Fratnik Steyera and Nataša Toplakc 


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.