L. Alharthi et al., MOLECULAR INHIBITION OF HIV TYPE-1 BY HIV TYPE-2 - EFFECTIVENESS IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS, AIDS research and human retroviruses, 14(1), 1998, pp. 59-64
HIV-2 downregulates HIV-1 in human primary peripheral blood mononuclea
r cells (PBMCs), Although the effect of HIV-2 on HIV-1 in human CD4(+)
T cell lines was previously reported, the present observations with P
BMCs are a necessary demonstration before considering animal model and
clinical studies, Notably, the downregulation was observed with at le
ast three phenotypically different HIV-1 proviruses and three differen
t HIV-2 proviruses and was independent of the mode of introduction of
the proviruses. HIV-2 inhibited both the production of extracellular H
IV-1 p24 antigen and intracellular viral RNA, suggesting the involveme
nt of transcriptional downmodulation, Some of the defective HIV-2 prov
iruses also inhibited HIV-1. In some cases, these defects mere transco
mplemented by the corresponding HIV-1 gene products, emphasizing cross
-regulation between the two viruses, The phenotype of one of the mutan
t 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 fo
r 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-der
ived gene transfer vectors may not only be inhibitory themselves but a
lso allow for the insertion of additional protective genes to aim at m
ultiple targets in the HIV-1 life cycle, thus curtailing the evolution
of escape mutants.