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
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Case Reports
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acquired Immunodeficiency Syndrome / mortality
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Acquired Immunodeficiency Syndrome / virology*
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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Line
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Cells, Cultured
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Chimera
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Chlorocebus aethiops
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DNA Primers
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DNA, Viral / metabolism
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Exons
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Gene Expression Regulation, Viral
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Gene Products, rev / biosynthesis*
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Gene Products, rev / genetics
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Genes, rev*
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Genome, Viral
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HIV Envelope Protein gp41 / biosynthesis*
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HIV Envelope Protein gp41 / genetics
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HIV Seronegativity / immunology
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HIV Seropositivity / virology*
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HIV-1 / genetics*
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HIV-1 / isolation & purification
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Homosexuality, Male
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Humans
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Interleukin-2 / pharmacology
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Kidney
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Lymphocytes / immunology*
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Lymphocytes / virology
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Macrophages / immunology
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Macrophages / virology
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Male
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Molecular Sequence Data
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Monocytes / immunology
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Monocytes / virology
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Mutagenesis, Site-Directed
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Oligodeoxyribonucleotides
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Polymerase Chain Reaction
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Proviruses / genetics
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / pharmacology
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Restriction Mapping
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Sequence Homology, Amino Acid
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Transfection
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beta-Galactosidase / biosynthesis
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rev Gene Products, Human Immunodeficiency Virus
Substances
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DNA Primers
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DNA, Viral
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Gene Products, rev
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HIV Envelope Protein gp41
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Interleukin-2
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Oligodeoxyribonucleotides
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Recombinant Proteins
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rev Gene Products, Human Immunodeficiency Virus
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beta-Galactosidase
Associated data
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GENBANK/U30730
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GENBANK/U30731
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GENBANK/U30732
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GENBANK/U30733
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GENBANK/U30734
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GENBANK/U30735
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GENBANK/U30736
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GENBANK/U30737
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GENBANK/U30738
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GENBANK/U30739
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GENBANK/U30740
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GENBANK/U30741
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GENBANK/U30742
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GENBANK/U30743
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GENBANK/U30744
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GENBANK/U30745
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GENBANK/U30746
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GENBANK/U30747
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GENBANK/U30748
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GENBANK/U30749
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GENBANK/U30750
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GENBANK/U30751
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GENBANK/U30752
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GENBANK/U30753
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GENBANK/U30754
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GENBANK/U30755
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GENBANK/U30756
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GENBANK/U30757
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GENBANK/U30758
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GENBANK/U30759