Sunday, May 12, 2019

JVI: Loss of Fitness in Mallards of Mexican HPAI H7N3 After Circulating in Chickens

Photo Credit SENASICA


Mexico has a long history of sporadic outbreaks of both LPAI (low pathogenic) and HPAI (Highly PathogenicH5 & H7 outbreaks, going back more than two decades. Large outbreaks have been fairly rare the past few years, but in 2012-2013 (see OIE: Mexico Reports HPAI H7N3 In Two States), H7N3 forced the culling of more than 22 million birds.
In 2018 Mexico: SENASICA Announced Several Outbreaks Of HPAI H7N3) , and again - starting early in 2019 (see OIE Report #2) - we've seen sporadic outbreaks in Mexican poultry.
Birds - waterfowl in particular - are the natural host for LPAI and (occasionally) HPAI viruses.  Often however, it is in poultry where LPAI viruses - introduced to them by migratory birds - mutate into a highly pathogenic form (see 2016's  LPAI-to-HPAI Mutation Cited in H7N8 Outbreak)

A study, published in 2016 (see Sci Repts.: Southward Autumn Migration Of Waterfowl Facilitates Transmission Of HPAI H5N1), suggests that waterfowl pick up new HPAI viruses in the spring (likely from poultry or terrestrial birds) on their way to their summer breeding spots - where they spread and potentially evolve - and then redistribute them on their southbound journey the following fall.
This cycle likely contributes to the growing diversity of both HPAI and LPAI viruses we've seen the past decade around the world.
But today we have a study that shows at least one HPAI virus - H7N3 in Mexico - not only adapted well to poultry, it has moved away from being well-adapted to its native host; mallard ducks.
While we've seen some avian flu viruses become more pathogenic, and highly transmissible in waterfowl (see Europe: Unusual Mortality Among Wild Birds From H5N8), in this case HPAI H7N3 - after several years passage through poultry - shows decreased fitness in mallards. 
This could help break the waterfowl-to-poultry-to-waterfowl transmission cycle of this virus, and in theory, help limit its spread.
Loss of fitness in mallards of Mexican H7N3 highly pathogenic avian influenza virus after circulating in chickens
Sung-Su Youk, Dong-Hun Lee, Christina M. Leyson, Diane Smith, Miria Ferreira Criado, Eric DeJesus, David E. Swayne, Mary J. Pantin-Jackwood
DOI: 10.1128/JVI.00543-19


Outbreaks of highly pathogenic avian influenza (HPAI) virus subtype H7N3 have been occurring in commercial chickens in Mexico since its first introduction in 2012. In order to determine changes in virus pathogenicity and adaptation in avian species, three H7N3 HPAI viruses from 2012, 2015, and 2016 were evaluated in chickens and mallards. All three viruses caused high mortality in chickens when given at medium to high doses and replicated similarly. No mortality or clinical signs and similar infectivity were observed in mallards inoculated with the 2012 and 2016 viruses.
However, the 2012 H7N3 HPAI virus replicated well in mallards and transmitted to contacts, whereas the 2016 virus replicated poorly and did not transmit to contacts, which indicates that the 2016 virus is less adapted to mallards. In vitro, the 2016 virus grew slower and to lower titers than the 2012 virus in duck fibroblast cells. Full genome sequencing showed 115 amino acid differences between the 2012 and the 2016 virus, with some of these changes previously associated with changes in replication in avian species including HA A125T, NP M105V and NP S377N.
In conclusion, as the Mexican H7N3 HPAI virus has passaged through large populations of chickens in a span of several years, it has retained its high pathogenicity for chickens but has decreased in fitness in mallards which could limit the potential spread of this HPAI virus by waterfowl.

Not much is known about changes in host adaptation of avian influenza (AI) viruses in birds after long-term circulation in chickens or other terrestrial poultry. Although the origin of AI viruses affecting poultry is wild aquatic birds, the role of these later birds in further dispersal of poultry-adapted AI viruses is not clear.
Previously, we showed that HPAI viruses isolated early from poultry outbreaks could still infect and transmit well in mallards. In this study, we demonstrate that the Mexican H7N3 HPAI virus after four years of circulation in chickens replicates poorly and does not transmit in mallards, but still remains highly pathogenic in chickens. This information on changes in host adaptation is important for understanding the epidemiology of AI viruses and the role that wild waterfowl may play in disseminating viruses adapted to terrestrial poultry.
This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

While the concern is always that an emerging novel virus will become a greater pandemic or epizootic threat over time, we've seen many instances where the threat from these viruses subsides. At least temporarily.
  • After jumping from Southeast Asia in 2004, and spreading to 60+ countries in Europe, Africa, and the Middle East by 2007 - H5N1 began a slow retreat in 2009. By 2012 it had pulled back from all but about a dozen countries.
In 2014, H5N1 returned to Africa (see EID Journal: HPAI A(H5N1) clade In West Africa), after an absence of almost 7 years.  Over the past couple of years we've seen a slow resurgence in Asia as well.  
While H5N1 still circulates in Indonesia, human cases have declined dramatically in recent years. This attenuation appears to be driven by the acquisition of genes from low pathogenicity avian influenza A virus progenitors.
  • H10N8 made a splash in late 2013 and early 2014, infecting three people in China, before going to ground.  It still circulates in birds, but hasn't caused a known human infection in 5 years.
  • H5N6 has been around since 2014, and has infected nearly 2 dozen people in china, but has failed to take off.  In Vietnam, and Laos, where the virus has also been detected, no human cases have been reported to date.

None of these viral threats is out of the running in the pandemic sweepstakes, but it does illustrate that evolution operates more or less on a trial and error basis - that failures and setbacks are common - and progress is rarely linear. 
While it could take years before the next potential pandemic virus wins the evolutionary lottery, it could just as easily happen today.  And once a virus obtains the right attributes to spread efficiently in humans, things will move quickly. 
All reasons why the current lull in avian flu activity around the world should be viewed as an opportunity to prepare, and not a permanent reprieve.  

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