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ARS Home » Southeast Area » Athens, Georgia » U.S. National Poultry Research Center » Exotic & Emerging Avian Viral Diseases Research » Research » Publications at this Location » Publication #335630
Title: Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A(H5N1) viruses in ferrets

Author
item PEARCE, MELISSA - Centers For Disease Control And Prevention (CDC) - United States
item GUSTIN, KORTNEY - Centers For Disease Control And Prevention (CDC) - United States
item PAPPAS, CLAUDIA - Centers For Disease Control And Prevention (CDC) - United States
item DAVID, TODD - Centers For Disease Control And Prevention (CDC) - United States
item Pantin Jackwood, Mary
item Swayne, David
item BELSER, JESSICA - Centers For Disease Control And Prevention (CDC) - United States
item TUMPEY, TERRENCE - Centers For Disease Control And Prevention (CDC) - United States

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/19/2016
Publication Date: 12/27/2016
Citation: Pearce, M.B., Gustin, K.M., Pappas, C., David, T., Pantin Jackwood, M.J., Swayne, D.E., Belser, J.A., Tumpey, T.M. 2016. Enhanced virulence of clade 2.3.2.1 highly pathogenic avian influenza A(H5N1) viruses in ferrets. Virology. 502:114-122.

Interpretive Summary: Highly pathogenic avian influenza (HPAI) H5N1 viruses sporadically transmit from avian species to humans. It is important to study currently circulating H5N1 influenza viruses to assess their potential risk. To better understand the pathogenesis associated with the continued diversification of clade 2 H5N1 influenza viruses, the virulence of several isolates collected from 2006-2013 from both poultry and human cases and their ability to cause disease in ferrets was investigated. Numerous clade 2 viruses were found to be of low virulence in the ferret model, but several clade 2.3.2.1 avian isolates tested produced severe disease and death in the ferrets. All H5N1 viruses replicated well in the respiratory tract, but lethal isolates replicated also in other tissues including the brain. The differences in virulence observed between the H5N1 viruses studied suggests there are distinct molecular determinants of virulence that once identified will help in surveillance and public health efforts against H5N1 viruses.

Technical Abstract: Sporadic avian to human transmission of highly pathogenic avian influenza (HPAI) A (H5N1) viruses necessitates the analysis of currently circulating and evolving clades to assess their potential risk. Following the spread and sustained circulation of clade 2 viruses across multiple continents, numerous subclades and genotypes have been described. To better understand the pathogenesis associated with the continued diversification of clade 2 H5N1 influenza viruses, we investigated the relative virulence of numerous isolates collected from 2006-2013 from both poultry and human cases and their ability to cause disease in the ferret model. Numerous clade 2 viruses, including a clade 2.2 avian isolate, a 2.2.2.1 human isolate, and two 2.2.1 human isolates, were found to be of low virulence in the ferret model, though lethality was detected following infection with one 2.2.1 human isolate. In contrast, three of six clade 2.3.2.1 avian isolates tested led to severe disease and death among infected ferrets. Clade 2.3.2.1b and 2.3.2.1c isolates, but not 2.3.2.1a isolates, were associated with ferret lethality. All H5N1 viruses replicated efficiently in the respiratory tract of ferrets regardless of their virulence and lethality. However, lethal isolates were characterized by systemic disease progression, including detection in the brain and enhanced histopathology in lung tissues. The finding of disparate virulence phenotypes between clade 2 H5N1 viruses, notably differences between subclades of 2.3.2.1 viruses, suggests there are distinct molecular determinants present within the established sub-groups, the identification of which will assist in molecular-based surveillance and public health efforts against H5N1 viruses.