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Trends Microbiol. 2018 Apr 19. pii: S0966-842X(18)30068-4. doi: 10.1016/j.tim.2018.03.005. [Epub ahead of print]
Influenza Hemagglutinin Protein Stability, Activation, and Pandemic Risk.
Russell CJ1, Hu M2, Okda FA2.
Author information
Abstract
For decades, hemagglutinin (HA) protein structure and its refolding mechanism have served as a paradigm for understanding protein-mediated membrane fusion. HA trimers are in a high-energy state and are functionally activated by low pH. Over the past decade, HA stability (or the pH at which irreversible conformational changes are triggered) has emerged as an important determinant in influenza virus host range, infectivity, transmissibility, and human pandemic potential. Here, we review HA protein structure, assays to measure its stability, measured HA stability values, residues and mutations that regulate its stability, the effect of HA stability on interspecies adaptation and transmissibility, and mechanistic insights into this process. Most importantly, HA stabilization appears to be necessary for adapting emerging influenza viruses to humans.
KEYWORDS:
fusion glycoprotein; influenza A virus; interspecies adaptation; pandemic; virus entry; virus transmission
PMID: 29681430 DOI: 10.1016/j.tim.2018.03.005
Influenza Hemagglutinin Protein Stability, Activation, and Pandemic Risk.
Russell CJ1, Hu M2, Okda FA2.
Author information
Abstract
For decades, hemagglutinin (HA) protein structure and its refolding mechanism have served as a paradigm for understanding protein-mediated membrane fusion. HA trimers are in a high-energy state and are functionally activated by low pH. Over the past decade, HA stability (or the pH at which irreversible conformational changes are triggered) has emerged as an important determinant in influenza virus host range, infectivity, transmissibility, and human pandemic potential. Here, we review HA protein structure, assays to measure its stability, measured HA stability values, residues and mutations that regulate its stability, the effect of HA stability on interspecies adaptation and transmissibility, and mechanistic insights into this process. Most importantly, HA stabilization appears to be necessary for adapting emerging influenza viruses to humans.
KEYWORDS:
fusion glycoprotein; influenza A virus; interspecies adaptation; pandemic; virus entry; virus transmission
PMID: 29681430 DOI: 10.1016/j.tim.2018.03.005