Sponsor
National Institutes of Health UM1-AI126617
Published In
PLoS Pathogens
Document Type
Article
Publication Date
9-1-2020
Subjects
HIV -- Case studies
Abstract
HIV Nef counteracts cellular host restriction factors SERINC3 and SERINC5, but our understanding of how naturally occurring global Nef sequence diversity impacts these activities is limited. Here, we quantify SERINC3 and SERINC5 internalization function for 339 Nef clones, representing the major pandemic HIV-1 group M subtypes A, B, C and D. We describe distinct subtype-associated hierarchies for Nef-mediated internalization of SERINC5, for which subtype B clones display the highest activities on average, and of SERINC3, for which subtype B clones display the lowest activities on average. We further identify Nef polymorphisms that modulate its ability to counteract SERINC proteins, including substitutions in the N-terminal domain that selectively impair SERINC3 internalization. Our findings demonstrate that the SERINC antagonism activities of HIV Nef differ markedly among major viral subtypes and between individual isolates within a subtype, suggesting that variation in these functions may contribute to global differences in viral pathogenesis.
Rights
Copyright (c) 2021 The Authors
This work is licensed under a Creative Commons Attribution 4.0 International License.
Locate the Document
DOI
10.1371/journal.ppat.1008813
Persistent Identifier
https://archives.pdx.edu/ds/psu/39056
Citation Details
Jin SW, Mwimanzi FM, MannJK, BwanaMB, Lee GQ, BrummeCJ, et al. (2020)VariationinHIV-1Nef function within and among viral subtypes reveals genetically separable antagonism of SERINC3and SERINC5.PLoSPathog16(9):e1008813.