Rev-independent simian immunodeficiency virus strains are nonpathogenic in neonatal macaques.

Published

Journal Article

The viral protein Rev is essential for the export of the subset of unspliced and partially spliced lentiviral mRNAs and the production of structural proteins. Rev and its RNA binding site RRE can be replaced in both human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) by the constitutive RNA transport element CTE of the simian type D retroviruses. We used neonatal macaques as a sensitive animal model to evaluate the pathogenicity of a pair of SIV mutant strains generated from Rev-independent molecular clones of SIVmac239 which differ only in the presence of the nef open reading frame. After high primary viremia, all animals remained persistently infected at levels below the threshold of detection. All macaques infected as neonates developed normally, and none showed any signs of immune dysfunction or disease during follow-up ranging from 2.3 to 4 years. Therefore, the Rev-RRE regulatory mechanism plays a key role in the maintenance of high levels of virus propagation, which is independent of the presence of nef. These data demonstrate that Rev regulation plays an important role in the pathogenicity of SIV. Replacement of Rev-RRE by the CTE provides a novel approach to dramatically lower the virulence of a pathogenic lentivirus. These data further suggest that antiretroviral strategies leading to even a partial block of Rev function may modulate disease progression in HIV-infected individuals.

Full Text

Duke Authors

Cited Authors

  • von Gegerfelt, AS; Liska, V; Li, P-L; McClure, HM; Horie, K; Nappi, F; Montefiori, DC; Pavlakis, GN; Marthas, ML; Ruprecht, RM; Felber, BK

Published Date

  • January 2002

Published In

Volume / Issue

  • 76 / 1

Start / End Page

  • 96 - 104

PubMed ID

  • 11739675

Pubmed Central ID

  • 11739675

International Standard Serial Number (ISSN)

  • 0022-538X

Digital Object Identifier (DOI)

  • 10.1128/jvi.76.1.96-104.2002

Language

  • eng

Conference Location

  • United States