Effects of vif mutations on cell-free infectivity and replication of simian immunodeficiency virus

In Woo Park, Kyl Myrick, Joseph Sodroski

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

To investigate the function of the Vif protein of the simian immunodeficiency virus (SIV), mutations were introduced into the SIVmac239 vif gene without affecting the reading frames of other overlapping genes. The phenotypes of these mutant viruses were examined with respect to viral replication and the expression and processing of viral proteins. Transfection of vif-mutant proviral DNA into established T cell lines resulted in a significant delay in the onset of virus replication compared to that seen with the wild-type provirus. The efficiency of replication of the vif-mutant virus was dependent on cell type. MT-4 cells were permissive for replication of the vif mutant, while replication in CEMxl74 cells was severely restricted. Little or no virus replication was observed following cell-free infection of the CEMxl74 cell line and macaque peripheral blood mononuclear cells (PBMC). These results indicate that the requirement for vif during the replication of SIVmac239 is dependent on cell type, as has been observed for HIV-1. Following cell-free infection, mutant viruses containing combined deletions in vif and the other regulatory genes (vpx, vpr, and nef) displayed replication kinetics similar to that of viruses containing the deletion of vif alone. Viral protein expression and processing in MT-4 cells of vif-deleted viruses were indistinguishable from those of the wild-type virus. The effects of two different point mutations in vif were examined. One point mutant in vif reverted to the genetic sequence of the wild-type virus within 2 weeks. A second point mutant that did not show genetic reversion displayed a similar kinetics of virus replication to that of the vif deletion mutant. These data show that impaired replication of vif mutant viruses results from mutation of the vif gene rather than the deletion of cis-acting elements, and also indicate that a strong selection exists against vif-defective viruses.

Original languageEnglish
Pages (from-to)1228-1236
Number of pages9
JournalJournal of Acquired Immune Deficiency Syndromes
Volume7
Issue number12
DOIs
StatePublished - Dec 1994

Keywords

  • Cell-free infectivity
  • Mutations
  • Replication
  • Simian immunodeficiency virus
  • Vif protein

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