Natural HIV-1 Nef Polymorphisms Impair SERINC5 Downregulation Activity.

ABSTRACT: HIV-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

SUBMITTER: Jin SW 

PROVIDER: S-EPMC6925589 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature