Monday, June 18, 2018

HPAI H5Nx Clade 2.3.4.4. Shedding In Cottontail Rabbits

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#13,370


Regular readers will recall that over the past several years we've been looking into the carriage of novel (and seasonal) flu by domestic and peridomestic animals, and how they might fit into the ecology and evolution of influenza viruses.

On the domestic front, dogs and cats take center stage, as both are susceptible to at least some novel flu strains.  A few (of many) blogs include:
mBio: Novel Reassortant Influenza A Viruses in Canines in Southern China
EID Journal: Avian H7N2 Virus in Human Exposed to Sick Cats

Study: Dogs As Potential `Mixing Vessels’ For Influenza
Korean CDC Statement On H5N6 In Cats

Influenza A(H6N1) In Dogs, Taiwan
On the peridomestic front, in recent years we've seen growing evidence that small mammals - like rabbits, skunks, mink, and even small rodents - can be infected by, and potentially spread, flu viruses.
While these types of animals may not pose as much as a direct threat of transmitting flu viruses to humans, they do provide a way for viruses in the wild to gain entry into farms, or to jump to dogs and cats.  
And carriage of novel flu viruses by any mammalian host provides the virus with an opportunity to develop host adaptations, potentially making it easier to jump to other mammals. 

A few past blogs include:
H9N2 Adaptation In Minks
Sci Rpts: Characterization of Avian H7N2 in Wild Birds and Pikas in Qinghai-Tibet Plateau Area
Taking HPAI To The Bank (Vole)
EID Journal: Guinea Pigs As Reservoirs For Influenza
One of the leaders in research into flu carriage and shedding by peridomestic animals is  Dr Jeffery Root - a Research Wildlife Biologist at the National Wildlife Research Center -  whose work we've been following for several years.
Which brings us to a new brief report (alas, mostly behind a pay wall) in the Archives of Virology, where Dr. Root et al. show that the HPAI H5 clade 2.3.4.4. virus - which sparked last year's European record setting epizootic - can infect cottontail rabbits, and that they can then shed the virus for one or more days. 
This is of particular interest since most clade 2.3.4.4. viruses - while causing huge losses in the poultry industry and among wild birds over the past four years - have shown a very limited ability to infect mammals. 
The exception (so far) being the HPAI H5N6 virus which has infected at least 17 people in China (see Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets).

First the (very) brief abstract, then I'll return with a bit more.

Cottontail rabbits shed clade 2.3.4.4 H5 highly pathogenic avian influenza A viruses
J. Jeffrey Root, Angela M. Bosco-Lauth, Nicole L. Marlenee, Richard A. Bowen
First Online: 13 June 2018

Abstract


During 2014-2015, clade 2.3.4.4 H5Nx highly pathogenic (HP) avian influenza A viruses (IAV) were first detected in North America and subsequently caused one of the largest agricultural emergencies in U.S. history.

Recent evidence has suggested that cottontail rabbits can shed multiple IAV subtypes. We experimentally infected cottontail rabbits with three HP H5Nx IAVs. All rabbits tested shed virus on at least one day by at least one route.

Cottontail rabbits appear to be an exception to the limited capacity for replication that has been previously reported for certain other mammalian species inoculated with clade 2.3.4.4 HP H5Nx avian influenza A viruses.

While clade 2.3.4.4. H5N8, H5N5 and (European Lineage) H5N6 viruses have not been shown to infect humans, we did see early reports out of South Korea in 2014 of dogs having been infected (see MAFRA: H5N8 Antibodies Detected In South Korean Dogs (Again)) and just over a year ago we looked at J. Vet. Sci.: Experimental Canine Infection With Avian H5N8.
So we know that mammalian infection with at least some genotypes of H5N8 is at least possible.  Today's report expands that host range a bit.
Over the past two years we've looked at a number of studies that have explored the potential for H5N8 or its spin offs to evolve into a human health threat. A few include:
J Vet Sci: Evolution, Global Spread, And Pathogenicity Of HPAI H5Nx Clade 2.3.4.4 
Study: Virulence Of HPAI H5N8 Enhanced By 2 Amino Acid Substitutions

Sci Rpts: H5N8 - Rapid Acquisition of Virulence Markers After Serial Passage In Mice 
Perhaps most telling of these came last September in J. Virulence : Altered Virulence Of (HPAI) H5N8 Reassortant Viruses In Mammalian Models, which found:
Taken together, our study demonstrates that a single gene substitution from other avian influenza viruses can alter the pathogenicity of recent H5N8 viruses, and therefore emphasizes the need for intensive monitoring of reassortment events among co-circulating avian and mammalian viruses.
Last October's J. Virulence Editorial: HPAI H5N8 - Should We Be Worried? reviewed and summarized the literature, and found enough reasons to be concerned over the future evolutionary path of H5N8, stating that:
The extensive distribution of HPAI H5N8, as well as the gene reassortment with other circulating avian viruses already observed for H5N8 suggests there is a potential risk for human cases of H5N8 infections.
While expanding H5's host range is always a concern, the ability of small mammals like rabbits, raccoons, and rodents to breach farm biosecurity measures, and infect poultry populations is also troubling.

And may require the the rethinking of some farm biosecurity measures in the future to prevent a repeat of 2016/17 epizootic.