Importance of the nef gene for maintenance of high virus loads and for development of AIDS

Cell. 1991 May 17;65(4):651-62. doi: 10.1016/0092-8674(91)90097-i.

Abstract

When rhesus monkeys were infected with a form of cloned SIVmac239 having a premature stop signal at the 93rd codon of nef, revertants with a coding codon at this position quickly and universally came to predominate in the infected animals. This suggests that there are strong selective forces for open functional forms of nef in vivo. Although deletion of nef sequences had no detectable effect on virus replication in cultured cells, deletion of nef sequences dramatically altered the properties of virus in infected rhesus monkeys. Our results indicate that nef is required for maintaining high virus loads during the course of persistent infection in vivo and for full pathologic potential. Thus, nef should become a target for antiviral drug development. Furthermore, the properties of virus with a deletion in nef suggest a means for making live-attenuated strains of virus for experimental vaccine testing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • Base Sequence
  • Cell Line
  • Chromosome Deletion
  • Cloning, Molecular
  • Codon / genetics
  • Genes, nef*
  • Humans
  • Macaca mulatta
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Simian Acquired Immunodeficiency Syndrome / immunology
  • Simian Acquired Immunodeficiency Syndrome / microbiology*
  • Simian Immunodeficiency Virus / genetics*
  • Simian Immunodeficiency Virus / physiology
  • Transfection
  • Virus Replication

Substances

  • Codon
  • Oligonucleotide Probes