Identification of key #hemagglutinin #residues responsible for #cleavage, acid stability, and #virulence of fifth-wave highly pathogenic #avian #influenza A(#H7N9) viruses (Virology, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Virology. 2019 Jul 12;535:232-240. doi: 10.1016/j.virol.2019.07.012. [Epub ahead of print]

Identification of key hemagglutinin residues responsible for cleavage, acid stability, and virulence of fifth-wave highly pathogenic avian influenza A(H7N9) viruses.

Sun X1, Belser JA1, Yang H1, Pulit-Penaloza JA1, Pappas C1, Brock N2, Zeng H1, Creager HM1, Stevens J1, Maines TR3.

Author information: 1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. 2 CNI Advantage LLC, Norman, OK, USA. 3 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address: tmaines@cdc.gov.

 

Abstract

We previously demonstrated that despite no airborne transmissibility increase compared to low pathogenic avian influenza viruses, select human isolates of highly pathogenic avian influenza A(H7N9) virus exhibit greater virulence in animal models and a lower threshold pH for fusion. In the current study, we utilized both in vitro and in vivo approaches to identify key residues responsible for hemagglutinin (HA) intracellular cleavage, acid stability, and virulence in mice. We found that the four amino acid insertion (-KRTA-) at the HA cleavage site of A/Taiwan/1/2017 virus is essential for HA intracellular cleavage and contributes to disease in mice. Furthermore, a lysine to glutamic acid mutation at position HA2-64 increased the threshold pH for HA activation, reduced virus stability, and replication in mice. Identification of a key residue responsible for enhanced acid stability of A(H7N9) viruses is of great significance for future surveillance activities and improvements in vaccine stability.

Copyright © 2019 Elsevier Inc. All rights reserved.

KEYWORDS: A(H7N9); Acid stability; Fusion; Hemagglutinin cleavage; Influenza virus; Mice; Virulence

PMID: 31325838 DOI: 10.1016/j.virol.2019.07.012

Keywords: Avian Influenza; H7N9; Viral pathogenesis; Animal models.

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gimi69

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.

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