Jin, SW;
Mwimanzi, FM;
Mann, JK;
Bwana, MB;
Lee, GQ;
Brumme, CJ;
Hunt, PW;
... Brockman, MA; + view all
(2020)
Variation in HIV-1 Nef function within and among viral subtypes reveals genetically separable antagonism of SERINC3 and SERINC5.
PLOS Pathogens
, 16
(9)
, Article e1008813. 10.1371/journal.ppat.1008813.
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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.
| Type: | Article |
|---|---|
| Title: | Variation in HIV-1 Nef function within and among viral subtypes reveals genetically separable antagonism of SERINC3 and SERINC5 |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.ppat.1008813 |
| Publisher version: | https://doi.org/10.1371/journal.ppat.1008813 |
| Language: | English |
| Additional information: | Copyright © 2020 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Cloning, HIV, Viral diseases, 293T cells, Flow cytometry, Pathogenesis, Virions, HIV-1 |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10112810 |
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