Variation in HIV-1 Nef function within and among viral subtypes reveals genetically separable antagonism of SERINC3 and SERINC5

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 pan...

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Bibliographic Details
Published in:PLoS pathogens 2020-09, Vol.16 (9), p.e1008813-e1008813
Main Authors: Jin, Steven W, Mwimanzi, Francis M, Mann, Jaclyn K, Bwana, Mwebesa Bosco, Lee, Guinevere Q, Brumme, Chanson J, Hunt, Peter W, Martin, Jeff N, Bangsberg, David R, Ndung'u, Thumbi, Brumme, Zabrina L, Brockman, Mark A
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
Authorship
Biology and Life Sciences
Cellular proteins
Cloning
Flow cytometry
Genetic aspects
Genetic polymorphisms
Health aspects
Health sciences
Hierarchies
HIV
Human immunodeficiency virus
Infections
Internalization
Medical research
Medicine
Medicine and Health Sciences
Nef protein
Pandemics
Pathogenesis
Proteins
Research and Analysis Methods
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1008813