@article{50545a5f197f4255b171bab528a7e5da,
title = "Variation in HIV-1 nef function within and among viral subtypes reveals genetically separable antagonism of serinc3 and serinc5",
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.",
author = "Jin, {Steven W.} and Mwimanzi, {Francis M.} and Mann, {Jaclyn K.} and Bwana, {Mwebesa Bosco} and Lee, {Guinevere Q.} and Brumme, {Chanson J.} and Hunt, {Peter W.} and Martin, {Jeff N.} and Bangsberg, {David R.} and Thumbi Ndung'u and Brumme, {Zabrina L.} and Brockman, {Mark A.}",
note = "Funding Information: This work was supported by the Canadian Institutes for Health Research (CIHR) (THA-118569, PJT-148621 and PJT-162123) and the National Institutes of Health, U.S.A. (UM1-AI126617). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. S.W.J. received the Frederick Banting and Charles Best Canada Graduate Scholarship Masters Award from CIHR. T.N. holds the South African Department of Science and Technology/National Research Foundation Research Chair in Systems Biology of HIV/AIDS. Z.L.B. is supported by a scholar award from the Michael Smith Foundation for Health Research. M.A.B. holds a Canada Research Chair, Tier 2, in viral pathogenesis and immunity. Publisher Copyright: {\textcopyright} 2020 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2020",
month = sep,
doi = "10.1371/journal.ppat.1008813",
language = "English (US)",
volume = "16",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "9",
}