Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity
AuthorsJin, Steven W.
Kuang, Xiaomei T.
Swann, Shayda A.
Gottlinger, Heinrich G.
Walker, Bruce D.
Brumme, Zabrina L.
Brockman, Mark A.
UMass Chan AffiliationsDepartment of Molecular, Cell and Cancer Biology
Amino Acids, Peptides, and Proteins
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AbstractHIV-1 Nef enhances virion infectivity by counteracting host restriction factor SERINC5; however, the impact of natural Nef polymorphisms on this function is largely unknown. We characterize SERINC5 downregulation activity of 91 primary HIV-1 subtype B nef alleles, including isolates from 45 elite controllers and 46 chronic progressors. Controller-derived Nef clones display lower ability to downregulate SERINC5 (median 80% activity) compared with progressor-derived clones (median 96% activity) (p = 0.0005). We identify 18 Nef polymorphisms associated with differential function, including two CTL escape mutations that contribute to lower SERINC5 downregulation: K94E, driven by HLA-B( *)08, and H116N, driven by the protective allele HLA-B( *)57. HIV-1 strains encoding Nef K94E and/or H116N display lower infectivity and replication capacity in the presence of SERINC5. Our results demonstrate that natural polymorphisms in HIV-1 Nef can impair its ability to internalize SERINC5, indicating that variation in this recently described function may contribute to differences in viral pathogenesis.
Cell Rep. 2019 Nov 5;29(6):1449-1457.e5. doi: 10.1016/j.celrep.2019.10.007. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/41267
RightsCopyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as Copyright 2019 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).