Biological variability of human immunodeficiency virus type-1 (HIV-1) is involved in the pathogenesis of acquired immunodeficiency syndrome (AIDS). Syncytium-inducing (SI) HIV-1 variants emerge in 50 percent of infected individuals during infection, preceding accelerated CD4+ T cell loss and rapid progression to AIDS. The V1 to V2 and V3 region of the viral envelope glycoprotein gp120 contained the major determinants of SI capacity. The configuration of a hypervariable locus in the V2 domain appeared to be predictive for non-SI to SI phenotype conversion. Early prediction of HIV-1 phenotype evolution may be useful for clinical monitoring and treatment of asymptomatic infection.
The causal relationship between HIVspecific CD4 ؉ T-cell responses and viral control and the effect of these responses on the natural history of HIV infection is unclear. In a detailed longitudinal study, functional HIV-1 Gag-specific CD4 ؉ T cells were analyzed in long-term asymptomatic individuals (LTA; n ؍ 6) and progressors to AIDS (n ؍ 7) with a median follow-up of, respectively, 118 and 57 months. Next, HIV-specific CD4 ؉ T-helper cell responses were measured in a prospective cohort study among 96 HIV seroconverters and were related to clinical endpoints using Cox proportional hazard analyses. In the detailed study, no difference for HIV-specific helper-cell responses between LTAs and progressors was observed early in infection, but Gagspecific CD4 ؉ T cells producing IL-2 or IFN␥ were lost in progressors late in infection. Multivariate proportional hazard analyses in the prospective cohort study showed that HIV-specific IL-2 ؉ , IFN␥ ؉ , or IL-2 ؉ IFN␥ ؉ CD4 ؉ T cells early after seroconversion had no prognostic value for the rate of progression to AIDS. Our results are compatible with viral load determining the nature and magnitude of HIV-specific CD4 ؉ T-cell responses, rather than HIV-specific CD4 ؉ T-cell responses controlling HIV plasma viral load. (Blood.
HIV-1 constructs harbouring a cleavage site mutation between protease and RT can probably act as trans-dominant negative mutants to interfere with wild-type viral replication.
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