Rare mutations in a domain crucial for V3-loop structure prevail in replicating HIV from long-term non-progressors.
AIDS
; 12(9): 985-97, 1998 Jun 18.
Article
en En
| MEDLINE
| ID: mdl-9662194
ABSTRACT
OBJECTIVE:
To evaluate the role of the selective forces exerted by the host on the HIV-1 structures involved in viral entry. DESIGN ANDMETHODS:
The V3 region of the env gene was analysed in cell-free HIV-1 RNA from 17 infectedsubjects:
11 long-term non-progressors (LTNP) and six symptomless, typical progressor patients. To evaluate the potential biological significance of one of the rare variants detected in the LTNP, it was reproduced by recombinant PCR into a HIV-1 molecular clone.RESULTS:
The intrapatient divergence of the V3-loop sequences averaged 8.62% in LTNP and 5.29% in progressors, although LTNP displayed lower divergence from the clade B consensus than progressors (16.65 and 19.76%, respectively). The analysis of non-synonymous and synonymous substitutions indicated that selective pressure was exerted in this region in both LTNP and progressors. Individual peculiarities (unique and rare V3-loop variants) emerged, however, in most sequences from LTNP, and variants bearing mutations in a domain crucial for the V3-loop structure were more prevalent in LTNP (P = 0.0012). The pNL4-3-derived mutant reproducing a V3-loop variant detected in a LTNP was efficiently expressed upon transfection, but the mutant virus was nearly completely unable to infect CD4+ cell lines, activated primary peripheral blood lymphocytes, or monocyte-derived macrophages, suggesting that a defect impaired the entry phase of the replication cycle.CONCLUSIONS:
The results indicate that host factors impose selective constraints on the evolution of the HIV-1 structures involved in viral entry. In LTNP, these factors are likely to force the virus into attenuated variants.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fragmentos de Péptidos
/
Replicación Viral
/
Proteína gp120 de Envoltorio del VIH
/
Infecciones por VIH
/
VIH-1
/
Receptores de Quimiocina
/
Mutación
Límite:
Humans
Idioma:
En
Revista:
AIDS
Asunto de la revista:
SINDROME DA IMUNODEFICIENCIA ADQUIRIDA (AIDS)
Año:
1998
Tipo del documento:
Article
País de afiliación:
Italia