Post entry determinants of primate lentivirus infectivity.

Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

Post entry determinants of primate lentivirus infectivity.

Conf Adv AIDS Vaccine Dev. 1997 May 4-7;:34. Unique Identifier : AIDSLINE MED/97927022
Stevenson M; Brichacek B; Jacque JM; Mann A; Sleigh R; Sharkey M; Sharova N; Lifson J; Hahn B; Hirsch V; University of Massachusetts Medical Center, Molecular Genetics and; Microbiology, Worcester, MA.

Abstract: Following fusion of viral with host cell membranes, viral nucleic acids are transported to the host cell nucleus where integration of viral with host cell DNA occurs. We have previously demonstrated that the structural gagMA protein and the Vpr/Vpx proteins are important in allowing viral nucleic acids to access the host cell nucleus. We have also demonstrated that the opposing membrane targeting and nuclear targeting properties of gagMA are regulated by phosphorylation and that this phosphorylation is carried out by a virion-associated serine/threonine kinase. We have now identified the virion-associated kinase as ERK-MAPK, a member of the mitogen-activated protein kinase cascade. The major virion substrate for this virion-associated kinase is gagMA. Virion-associated MAPK activity and virus infectivity can be stimulated in trans with PMA or a dominant active MAP kinase MEK). In contrast, virion-associated MAPK activity and virus infectivity can be inhibited by specific inhibitors of the MAP kinase pathway. Nef does not appear to directly influence the activation of MAP kinase components but is able to activate a Src family tyrosine kinase which regulates the MAP kinase cascade. In addition to gagMA, nuclear transport of viral reverse transcription complexes is facilitated by HIV-1 Vpr while in SIV(sm)PBj, this function is provided by Vpx. SIV(sm)PBj Vpx mutants replicate efficiently in activated macaque T cells but are unable to replicate in macaque macrophages. We have studied in vivo properties of SIV(sm)PBj Vpr and Vpx mutants in nemestrina macaques in order to examine the role of macrophages in viral pathogenicity. Our studies support the notion that macrophages play an essential role in mucosal transmission and additionally in virus dissemination and persistence.

Keywords: *HIV-1/PATHOGENICITY *Membrane Fusion
971130
M97B1196

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