CD4-independent infection by human immunodeficiency virus type 1 after phenotypic mixing with human T-cell leukemia viruses.
Although human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome and related disorders, it has been suggested that viral cofactors may accelerate the progression of the disease. We present evidence that human T lymphoid cells productively coinfected by HIV type 1 (HIV-1) and human T-cell leukemia virus type I (HTLV-I) or HTLV-II generate a progeny of phenotypically mixed viral particles that allow the penetration of HIV-1 into previously nonsusceptible CD4- human cells, including mature CD8+ T lymphocytes, B lymphoid cells, epithelial cells, and skeletal muscle cells. The infection is independent of the major HIV-1 receptor, (i.e., the CD4 glycoprotein) since OKT4a, a neutralizing anti-CD4 monoclonal antibody, fails to block the penetration of HIV-1. Similarly, infection is not inhibited by monoclonal antibody M77, directed toward the neutralizing loop of the gp120 envelope glycoprotein of HIV-1. In contrast, pretreatment of the virus stock with HTLV-I-neutralizing human serum completely abolishes the penetration of phenotypically mixed HIV-1 into CD4- cells. These results suggest that HTLV-I or HTLV-II may increase the pathogenicity of HIV-1 by broadening the spectrum of its cellular tropism and, thus, favoring its spread within the organism of coinfected hosts.
Lusso
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P
Laboratory of Tumor Cell Biology, National Cancer Institute, Bethesda, Maryland 20892.
Lori
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F
Gallo
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RC
D001483:Base Sequence; D015704:CD4 Antigens; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D015367:Human T-lymphotropic virus 2 / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D015345:Oligonucleotide Probes; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D015704:CD4 Antigens; D004279:DNA, Viral; D015345:Oligonucleotide Probes