Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
Human immunodeficiency virus (HIV) type 2-mediated inhibition of HIV type 1: a new approach to gene therapy of HIV-infection.
Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4486-91. Unique Identifier : AIDSLINE MED/96210671 Arya SK; Gallo RC; Laboratory of Tumor Cell Biology, National Cancer Institute,; National Institutes of Health, Bethesda, MD 20892-4255, USA.
Abstract:
Human immunodeficiency virus (HIV) type 2, the second AIDS-associated human retrovirus, differs from HIV-1 in its natural history, infectivity, and pathogenicity, as well as in details of its genomic structure and molecular behavior. We report here that HIV-2 inhibits the replication of HIV-1 at the molecular level. This inhibition was selective, dose-dependent, and nonreciprocal. The closely related simian immunodeficiency provirus also inhibited HIV-1. The selectivity of inhibition was shown by the observation that HIV-2 did not significantly downmodulate the expression of the unrelated murine leukemia virus; neither did the murine leukemia virus markedly affect HIV-1 or HIV-2 expression. Moreover, while HIV-2 potently inhibited HIV-1, the reverse did not happen, thus identifying yet another and remarkable difference between HIV-1 and HIV-2. Mutational analysis of the HIV-2 genome suggested that the inhibition follows a complex pathway, possibly involving multiple genes and redundant mechanisms. Introduction of inactivating mutations into the structural and regulatory/accessory genes did not render the HIV-2 provirus ineffective. Some of the HIV-2 gene defects, such as that of tat and rev genes, were phenotypically transcomplemented by HIV-1. The HIV-2 proviruses with deletions in the putative packaging signal and defective for virus replication were effective in inducing the suppressive phenotype. 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. Induction of a cytokine is another possibility. These findings might be relevant to the clinical-epidemiological data suggesting that infection with HIV-2 may offer some protection against HIV-1 infection.
Keywords: Acquired Immunodeficiency Syndrome/*THERAPY Animal Cloning, Molecular Comparative Study CD4-Positive T-Lymphocytes/IMMUNOLOGY/*VIROLOGY Gene Expression Regulation, Viral Gene Therapy/*METHODS Genes, rev Genes, tat Genes, Regulator Genes, Structural, Viral Genes, Viral Human HIV-1/GENETICS/*PHYSIOLOGY HIV-2/GENETICS/*PHYSIOLOGY Leukemia Viruses, Murine/PHYSIOLOGY Mice Proviruses/PHYSIOLOGY Sequence Deletion Species Specificity SIV/PHYSIOLOGY Transfection *Virus Replication JOURNAL ARTICLE 960930
M9690883
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
