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Title: Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses

Journal Article · · Journal of Virology
DOI:https://doi.org/10.1128/JVI.00180-16· OSTI ID:1257478
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2]
  1. Centers for Disease Control and Prevention, Atlanta, GA (United States)
  2. St. Jude Children's Research Hospital, Knoxville, TN (United States)

During 2014, a subclade 2.3.4.4 highly pathogenic avian influenza (HPAI) A(H5N8) virus caused poultry outbreaks around the world. In late 2014/early 2015, the virus was detected in wild birds in Canada and the United States, and these viruses also gave rise to reassortant progeny, composed of viral RNA segments (vRNAs) from both Eurasian and North American lineages. In particular, viruses were found with N1, N2, and N8 neuraminidase vRNAs, and these are collectively referred to as H5Nx viruses. In the United States, more than 48 million domestic birds have been affected. Here we present a detailed structural and biochemical analysis of the surface antigens of H5N1, H5N2, and H5N8 viruses in addition to those of a recent human H5N6 virus. Our results with recombinant hemagglutinin reveal that these viruses have a strict avian receptor binding preference, while recombinantly expressed neuraminidases are sensitive to FDA-approved and investigational antivirals. Although H5Nx viruses currently pose a low risk to humans, it is important to maintain surveillance of these circulating viruses and to continually assess future changes that may increase their pandemic potential. The H5Nx viruses emerging in North America, Europe, and Asia pose a great public health concern. Here we report a molecular and structural study of the major surface proteins of several H5Nx influenza viruses. Furthermore, our results improve the understanding of these new viruses and provide important information on their receptor preferences and susceptibilities to antivirals, which are central to pandemic risk assessment.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); National Inst. of General Medical Sciences; HHS; Center for Disease Control and Prevention (CDC)
Grant/Contract Number:
AC02-06CH11357; GM62116
OSTI ID:
1257478
Journal Information:
Journal of Virology, Vol. 90, Issue 12; ISSN 0022-538X
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
ENGLISH
Citation Metrics:
Cited by: 47 works
Citation information provided by
Web of Science

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A Naturally Occurring Deletion in the Effector Domain of H5N1 Swine Influenza Virus Nonstructural Protein 1 Regulates Viral Fitness and Host Innate Immunity journal March 2018
Structure of an Influenza A virus N9 neuraminidase with a tetrabrachion-domain stalk journal January 2019
A study of the relationship between human infection with avian influenza a (H5N6) and environmental avian influenza viruses in Fujian, China journal September 2019
Full sequence analysis of hemagglutinin and neuraminidase genes and proteins of highly pathogenic avian influenza H5N1 virus detected in Iran, 2015 journal October 2018
Altered virulence of Highly Pathogenic Avian Influenza (HPAI) H5N8 reassortant viruses in mammalian models journal September 2017
Metabolic machinery encrypted in the Raman spectrum of influenza A virus‐inoculated mammalian cells journal November 2019
The Emergence and Decennary Distribution of Clade 2.3.4.4 HPAI H5Nx journal May 2019
Heterologous prime-boost with A(H5N1) pandemic influenza vaccines induces broader cross-clade antibody responses than homologous prime-boost journal May 2019
Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets journal January 2018
Identification of antigenic epitopes in the haemagglutinin protein of H7 avian influenza virus journal October 2019
Comparison of the pathogenic potential of highly pathogenic avian influenza (HPAI) H5N6, and H5N8 viruses isolated in South Korea during the 2016–2017 winter season journal December 2018
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