Inhibition of HIV-1 expression by HIV-2

Abstract

HIV-1 and HIV-2 are co-endemic in certain geographic areas. HIV-2 is more weakly pathogenic than HIV-1, and progression to AIDS occurs less frequently and over a longer period of time. Recent epidemiologic studies suggest that individuals infected with HIV-2 have a lower risk of HIV-1 infection. Both immune mechanisms and various modes of viral interference have been proposed to account for these results. Our findings, described in this paper, suggest that HIV-2 inhibits HIV-1 replication. To study the molecular interactions between HIV-1 and HIV-2, proviral clones were transfected alone or in combination into the human T cell line CEM. LTR-CAT indicator constructs were included for the purpose of monitoring viral promoter activity. Viral replication in transfected cells was monitored by p24 antigen capture assay of cell culture supernatants and Western blot analysis of cell extracts. HIV-2 inhibited HIV-1 replication as determined by intracellular and extracellular p24 antigen levels. Similar results were obtained with simultaneous virus infection using HIV-1 and HIV-2, rather than transfections of proviral DNA. Using cotransfection of HIV-1 and HIV-2 LTR indicator gene constructs, the mechanism of inhibition was found to be suppression of the HIV-1 LTR by HIV-2. The inhibitory effect of HIV-2 is not due to Tat-2, but appears to discriminate between the HIV-1 and HIV-2 LTRs based on differences in the Tat activation response element, TAR. These results suggest both a molecular mechanism for HIV-2 interference with HIV-1 replication and a potential molecular approach to therapy.

Interactions of HIV-1 and HIV-2 in West Africa.

“…Though the exact mechanism remains to be defined, the inhibition appeared to be mainly due to an intracellular molecular event because it could not be explained solely on the basis of cell surface receptor mediated interference. The results support the notion that the inhibition likely occurred at the level of viral RNA, possibly involving competition between viral RNAs for some transcriptional factor essential for virus replication [77,78].…”

Mortality rates in people dually infected with HIV-1/2 and those infected with either HIV-1 or HIV-2

“…In contrast, a meta-analysis showed that HIV-2-infected individuals are more likely to acquire HIV-1 infection than HIV-negative individuals [38]. Several laboratory studies suggested that in dually infected individuals, HIV-2 exerted a possible inhibitory effect on HIV-1 disease progression [20,[40][41][42][43], but other studies found no effect of HIV-2 on the viral load of HIV-1 [34,44]. In this meta-analysis, we did not find evidence for an inhibitory effect, as there was no significant difference between mortality rates for HIV-D and HIV-1.…”

The sequence and structure of the 3' arm of the first stem-loop of the human immunodeficiency virus type 2 trans-activation responsive region mediate Tat-2 transactivation

“…Further characterization of this factor, which appears to be necessary for Tat-2, but not necessarily for Tat-1 to transactivate through TAR-2, should yield insight into the differences between the mechanisms of action of Tat-1 and Tat-2 and into how the crucial Tat transactivators function in general. In view of recent reports that HIV-2 inhibits HIV-1 expression (50a), an effect perhaps mediated by TAR (36), an understanding of TAR-2-mediated transactivation may suggest therapeutic modalities for HIV-1, as well as for HIV-2.…”