The Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission.

The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines

CD3+CD8+ cell levels as predictors of transmission in human immunodeficiency virus-infected couples: A report from the heterosexual HIV transmission study

AbstractObjective: The goal of this study was to identify in human immunodeficiency virus (HIV)-infected individuals immunologic markers that correlated with transmission of HIV by heterosexual contact.Methods: In a case-control comparison of couples, immunologic and viral parameters were evaluated in 343 HIV-positive individuals who were members of 67 HIV-seroconcordant couples (both partners HIV positive) and 211 HIV serodiscordant couples (one positive, one negative).Results: The most striking immunologic finding was the increased numbers of CD3+CD8+ cells found in the index member of discordant couples as compared to the index member of the concordant couples. Differences in CD3+CD8+ levels persisted after adjustment for stage of disease and CD3+CD4+ count. This increase in the number of CD3+CD8+ cells was accompanied by a concomitant decrease in the amount of viral replication measured by both HIV culture endpoint and quantitative RNA polymerase chain reaction (PCR).Conclusion: Data presented here further support the role of CD3+CD8+ cells in suppressing or controlling viral activity, although a causal role based on case-control data must be advanced cautiously. This in vivo biologic function may help prevent or lower the risk of HIV transmission