Short Communication : Molecular Inhibition of HIV Type 1 by HIV Type 2: Effectiveness in Peripheral Blood Mononuclear Cells

Abstract

HIV-2 downregulates HIV-1 in human primary peripheral blood mononuclear cells (PBMCs). Although the effect of HIV-2 on HIV-1 in human CD4⁺ T cell lines was previously reported, the present observations with PBMCs are a necessary demonstration before considering animal model and clinical studies. Notably, the downregulation was observed with at least three phenotypically different HIV-1 proviruses and three different HIV-2 proviruses and was independent of the mode of introduction of the proviruses. HIV-2 inhibited both the production of extracellular HIV-1 p24 antigen and intracellular viral RNA, suggesting the involvement of transcriptional downmodulation. Some of the defective HIV-2 proviruses also inhibited HIV-1. In some cases, these defects were transcomplemented by the corresponding HIV-1 gene products, emphasizing cross-regulation between the two viruses. The phenotype of one of the mutant HIV-2 proviruses suggested that the posttranscriptional effects may also occur. In addition to the possible HIV-2 suppression of HIV-1 in vivo by cross-protective immune mechanisms, intracellular inhibition, noted here, may be another line of defense. We have proposed that the inhibition may be the result of competition between HIV-1 and HIV-2 for cellular factors, possibly involving the long terminal repeats (LTRs). For safety reasons, it may be advantageous to use subunits of HIV-2 for vaccines and gene therapy. HIV-2, specifically noncytopathic HIV-2, could be viewed as an attenuated HIV-1 vaccination model. HIV-2-derived gene transfer vectors may not only be inhibitory themselves but also allow for the insertion of additional protective genes to aim at multiple targets in the HIV-1 life cycle, thus curtailing the evolution of escape mutants.