HIV-1 adaptation to low levels of CCR5 results in V3 and V2 loop changes that increase envelope pathogenicity, CCR5 affinity and decrease susceptibility to Maraviroc.
Virology
; 493: 86-99, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-27017055
ABSTRACT
Variability in CCR5 levels in the human population is suggested to affect virus evolution, fitness and the course of HIV disease. We previously demonstrated that cell surface CCR5 levels directly affect HIV Envelope mediated bystander apoptosis. In this study, we attempted to understand HIV evolution in the presence of low levels of CCR5, mimicking the limiting CCR5 levels inherent to the host. HIV-1 adaptation in a T cell line expressing low levels of CCR5 resulted in two specific mutations; N302Y and E172K. The N302Y mutation led to accelerated virus replication, increase in Maraviroc IC50 and an increase in Envelope mediated bystander apoptosis in low CCR5 expressing cells. Analysis of subtype B sequences showed that N302Y is over-represented in CXCR4 tropic viruses in comparison to CCR5 tropic isolates. Considering the variability in CCR5 levels between individuals, our findings have implications for virus evolution, MVC susceptibility as well as HIV pathogenesis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteína gp120 do Envelope de HIV
/
HIV-1
/
Receptores CCR5
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article