A molecular clone of HTLV-III with biological activity.
Acquired immune deficiency syndrome (AIDS) is an epidemic immunosuppressive disease characteristically associated with a depletion of T lymphocytes of the helper/inducer phenotype. Numerous converging lines of research have implicated a human T-cell lymphotropic retrovirus, HTLV-III, in the pathogenesis of AIDS. Recently, several distinct forms of the HTLV-III genome were molecularly cloned in phage and extensively characterized. In the present study, a clone containing full-length HTLV-III proviral DNA was inserted into a plasmid and used to transfect cord blood T cells from normal newborn humans. We demonstrate that this molecular clone is infectious in vitro and causes marked cytopathic effects on T-cell cultures. This is the first direct evidence that the HTLV-III genome, rather than a minor component of the virus complex, is cytopathic for T cells. Using this biologically competent clone and mutants derived from it, it should now be possible to localize the subgenomic regions that contribute to the biological effects of HTLV-III.
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AG
Fisher
E
E
Collalti
L
L
Ratner
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RC
Gallo
F
F
Wong-Staal
D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D000956:Antigens, Viral / Q000235:genetics; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003588:Cytopathogenic Effect, Viral; D004279:DNA, Viral / Q000096:biosynthesis; D017977:Deltaretrovirus / Q000235:genetics*; D015683:Gene Products, gag; D006801:Humans; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D013601:T-Lymphocytes / Q000382:microbiology*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication
D000956:Antigens, Viral; D004279:DNA, Viral; D015683:Gene Products, gag; D014764:Viral Proteins; D012194:RNA-Directed DNA Polymerase