Persistence of attenuated rev genes in a human immunodeficiency virus type 1-infected asymptomatic individual

J Virol. 1995 Sep;69(9):5743-53. doi: 10.1128/JVI.69.9.5743-5753.1995.

Abstract

With the goal of examining the functional diversity of human immunodeficiency virus type 1 (HIV-1) env genes within the peripheral blood mononuclear cells of an asymptomatic individual, we substituted four complete env genes into the replication-competent NL4-3 provirus. Despite encoding full-length open reading frames for gp120 and gp41 and the second coding exon of tat and rev, each chimera was replication defective. Site-directed mutagenesis of codon 78 in the Rev activation domain (from a hitherto unique Ile to the subtype B consensus Leu) partially restored infectivity for two of three chimeras tested. Similarly, mutagenesis of rev codon 78 of NL4-3 from Leu to Ile partially attenuated this virus. Ile-78 was found in all 13 clones examined from samples taken from this asymptomatic subject 4.5 years after infection, including 9 from peripheral blood mononuclear cells and 4 from a virus isolate, as well as 4 additional clones each from peripheral blood mononuclear cells sampled 37 and 51 months later. We next examined conservation of the Rev activation domain within and among long-term survivors (LTS) and patients with AIDS, as well as T-cell-line-adapted strains of HIV-1. Putative attenuating mutations were found in a minority of sequences from all five LTS and two of four patients with AIDS. Of the 11 T-cell-line-adapted viruses examined, none had these changes. Among and within LTS virus population had marginally higher levels of diversity in Rev than in Env; patients with AIDS had similar levels of diversity in the two reading frames; and T-cell-line-adapted viruses had higher levels of diversity in Env. These results are consistent with the hypothesis that asymptomatic individuals harbor attenuated variants of HIV-1 which correlate with and contribute to their lack of disease progression.

Publication types

  • Case Reports
  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / mortality
  • Acquired Immunodeficiency Syndrome / virology*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • Cells, Cultured
  • Chimera
  • Chlorocebus aethiops
  • DNA Primers
  • DNA, Viral / metabolism
  • Exons
  • Gene Expression Regulation, Viral
  • Gene Products, rev / biosynthesis*
  • Gene Products, rev / genetics
  • Genes, rev*
  • Genome, Viral
  • HIV Envelope Protein gp41 / biosynthesis*
  • HIV Envelope Protein gp41 / genetics
  • HIV Seronegativity / immunology
  • HIV Seropositivity / virology*
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Homosexuality, Male
  • Humans
  • Interleukin-2 / pharmacology
  • Kidney
  • Lymphocytes / immunology*
  • Lymphocytes / virology
  • Macrophages / immunology
  • Macrophages / virology
  • Male
  • Molecular Sequence Data
  • Monocytes / immunology
  • Monocytes / virology
  • Mutagenesis, Site-Directed
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction
  • Proviruses / genetics
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / pharmacology
  • Restriction Mapping
  • Sequence Homology, Amino Acid
  • Transfection
  • beta-Galactosidase / biosynthesis
  • rev Gene Products, Human Immunodeficiency Virus

Substances

  • DNA Primers
  • DNA, Viral
  • Gene Products, rev
  • HIV Envelope Protein gp41
  • Interleukin-2
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • rev Gene Products, Human Immunodeficiency Virus
  • beta-Galactosidase

Associated data

  • GENBANK/U30730
  • GENBANK/U30731
  • GENBANK/U30732
  • GENBANK/U30733
  • GENBANK/U30734
  • GENBANK/U30735
  • GENBANK/U30736
  • GENBANK/U30737
  • GENBANK/U30738
  • GENBANK/U30739
  • GENBANK/U30740
  • GENBANK/U30741
  • GENBANK/U30742
  • GENBANK/U30743
  • GENBANK/U30744
  • GENBANK/U30745
  • GENBANK/U30746
  • GENBANK/U30747
  • GENBANK/U30748
  • GENBANK/U30749
  • GENBANK/U30750
  • GENBANK/U30751
  • GENBANK/U30752
  • GENBANK/U30753
  • GENBANK/U30754
  • GENBANK/U30755
  • GENBANK/U30756
  • GENBANK/U30757
  • GENBANK/U30758
  • GENBANK/U30759