tetano
Editor, Senior Moderator
J Virol. 2014 Oct 15. pii: JVI.01927-14. [Epub ahead of print]
Variation of pH sensitivity, acid stability, and fusogenicity of three influenza H3 subtypes.
Costello DA1, Whittaker GR2, Daniel S3.
Author information
Abstract
Influenza A virus strains adapt to achieve successful entry into host species. Entry is mediated by the viral membrane protein, hemagglutinin (HA), which triggers membrane fusion and genome release under acidic conditions in the endosome. In addition to changes in the receptor binding domain, the acid stability of HA has been linked to successful transmission of virus between avian and human hosts. However, to fully understand the connection between changes in HA and host tropism, additional factors relevant to HA structure-function and membrane fusion are also likely to be important. Using single particle tracking (SPT) techniques, individual membrane fusion events can be observed under specific conditions, which provides detailed information regarding HA pH sensitivity, acid stability, and the rate and extent of membrane fusion. This provides a comparative way to characterize and distinguish influenza fusion properties among virus strains. We used SPT to quantify the fusion properties of three H3 influenza strains: A/Aichi/68/H3N2 (X:31), A/Udorn/72/H3N2 (Udorn) and A/Brisbane/07/H3N2 (Brisbane). The rate of fusion for the most clinically relevant strain, Brisbane, is generally insensitive to decreasing pH, while fusion of the egg-adapted strains, Udorn and X:31, are strongly dependent on pH (and faster) as pH decreases. All strains exhibit similar acid stability (the length of time they remain fusogenic in an acidic environment) at higher pH's, but the egg-adapted strains become less acid stable at lower pH's. Thus, it appears that the lab-adapted H3 strains tested may have evolved to compensate for the faster HA deactivation at low pH with a commensurate increase in the rate of fusion and number of proteins facilitating fusion, relative to the Brisbane strain.
IMPORTANCE:
The ability of influenza virus to release its genome under different acidic conditions has recently been linked to transmission of influenza virus between different species. However, it is yet to be determined how acid-induced membrane fusion varies with virus strain and influences tropism. The results presented here are an intra-H3 subtype study of acid stability and fusion kinetics. Using a single particle tracking (SPT) technique, we show here that the highest pH that initiates fusion is not necessarily the pH where the kinetics of fusion is fastest and most abundant for a given strain. Strains exhibit different fusion behaviors, as evidenced by their unique kinetic trends; pH sensitivities, as evidenced by the differences when the first fusion events commence; and HA stabilities, as evidenced by the length of time virions can persist in acidic environment and still be fusion competent.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25320308
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25320308
Variation of pH sensitivity, acid stability, and fusogenicity of three influenza H3 subtypes.
Costello DA1, Whittaker GR2, Daniel S3.
Author information
Abstract
Influenza A virus strains adapt to achieve successful entry into host species. Entry is mediated by the viral membrane protein, hemagglutinin (HA), which triggers membrane fusion and genome release under acidic conditions in the endosome. In addition to changes in the receptor binding domain, the acid stability of HA has been linked to successful transmission of virus between avian and human hosts. However, to fully understand the connection between changes in HA and host tropism, additional factors relevant to HA structure-function and membrane fusion are also likely to be important. Using single particle tracking (SPT) techniques, individual membrane fusion events can be observed under specific conditions, which provides detailed information regarding HA pH sensitivity, acid stability, and the rate and extent of membrane fusion. This provides a comparative way to characterize and distinguish influenza fusion properties among virus strains. We used SPT to quantify the fusion properties of three H3 influenza strains: A/Aichi/68/H3N2 (X:31), A/Udorn/72/H3N2 (Udorn) and A/Brisbane/07/H3N2 (Brisbane). The rate of fusion for the most clinically relevant strain, Brisbane, is generally insensitive to decreasing pH, while fusion of the egg-adapted strains, Udorn and X:31, are strongly dependent on pH (and faster) as pH decreases. All strains exhibit similar acid stability (the length of time they remain fusogenic in an acidic environment) at higher pH's, but the egg-adapted strains become less acid stable at lower pH's. Thus, it appears that the lab-adapted H3 strains tested may have evolved to compensate for the faster HA deactivation at low pH with a commensurate increase in the rate of fusion and number of proteins facilitating fusion, relative to the Brisbane strain.
IMPORTANCE:
The ability of influenza virus to release its genome under different acidic conditions has recently been linked to transmission of influenza virus between different species. However, it is yet to be determined how acid-induced membrane fusion varies with virus strain and influences tropism. The results presented here are an intra-H3 subtype study of acid stability and fusion kinetics. Using a single particle tracking (SPT) technique, we show here that the highest pH that initiates fusion is not necessarily the pH where the kinetics of fusion is fastest and most abundant for a given strain. Strains exhibit different fusion behaviors, as evidenced by their unique kinetic trends; pH sensitivities, as evidenced by the differences when the first fusion events commence; and HA stabilities, as evidenced by the length of time virions can persist in acidic environment and still be fusion competent.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
25320308
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25320308