Viral genetic determinants in SIVsmmPBj pathogenesis.

Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.

Viral genetic determinants in SIVsmmPBj pathogenesis.

Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 30. Unique Identifier : AIDSLINE PRIM11/94191624
Novembre FJ; Hirsch VM; Lewis MG; Johnson PR; Klumpp S; Anderson DC; McClure HM; Yerkes Regional Primate Research Center, Atlanta, GA.

Abstract: SIVsmmPBj (PBj) induces an acutely lethal disease when inoculated into pigtailed macaques. This disease syndrome, characterized by a fulminant diarrhea, acidosis and wasting, has been likened to a cytokine induced enteritis. As a means to investigate the molecular basis of PBj-induced disease, we have utilized molecular clones of PBj that reproduce this lethal disease as a tool to dissect genetic elements involved in the induction of this acute disease. Analyses utilizing chimeric viruses, constructed between one of our acutely lethal PBj clones (PBj6.6) and SIVsmH4, suggested that multiple genetic determinants were involved in the increased pathogenesis of PBj-induced disease. In particular, sequences located in the env gene, but not the duplicated NF-kappa B site, were required for development of acutely lethal disease. Results utilizing additional constructs suggested that a determinant in the 5' half of the PBj genome also contributes to virulence. To examine the role of the 5' half in the pathogenesis of PBj, we have generated chimeras containing either the gag gene or the pol gene of SIVsmH4 (PBj6.6/smH4gag, PBj6.6/smH4pol, respectively). Only virus derived from the PBj6.6/smH4pol construct was able to induce acute disease in inoculated macaques. Virus derived from a chimera containing the central regulatory genes of SIVsmH4 (vif, vpx, vpr, tat and rev) was not able to induce death. These results indicate that a complex set of viral determinants are involved in PBj pathogenesis. In our studies, we have found that the ability of a virus to induce proliferation of macaque PBMC in vitro is associated with its ability to induce acute disease, but not necessarily its ability to replicate well in macrophages. Additional chimeras constructed by exchange of regions encoding gp120 and gp40 have been derived and will be useful in dissecting the important genetic determinants in the env gene of PBj.

Keywords: Animal Chimera Cloning, Molecular Genes, env Genes, gag Genes, pol Genes, Regulator *Genes, Viral Macaca nemestrina Simian Acquired Immunodeficiency Syndrome/*MICROBIOLOGY Support, U.S. Gov't, P.H.S. SIV/*GENETICS/*PATHOGENICITY Virulence/GENETICS ABSTRACT
940730
M9470894

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