Variation in HIV-1 Nef function within and among viral subtypes reveals genetically separable antagonism of SERINC3 and SERINC5.
PLoS Pathog
; 16(9): e1008813, 2020 09.
Article
in En
| MEDLINE
| ID: mdl-32925973
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Virus Replication
/
Membrane Glycoproteins
/
HIV Infections
/
HIV-1
/
Nef Gene Products, Human Immunodeficiency Virus
/
Membrane Proteins
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
PLoS Pathog
Year:
2020
Type:
Article
Affiliation country:
Canada