Activation of tat-defective human immunodeficiency virus by ultraviolet light.
Ultraviolet light (UV) is known to cause activation of gene expression from the human immunodeficiency virus type 1 (HIV-1) promoter. To address the question of whether tat-defective HIV-1 provirus could be rescued by UV irradiation we examined its effect on HeLa cells containing integrated proviruses with tat mutations. Exposure of these cells to an optimal dose of UV resulted in the production of infectious viruses. The degree of UV activation and reversion to infectious virus appeared to depend on the nature of the original tat mutation. Two of the mutants required cocultivation with tat-expressing cells to fully generate replication competent viruses, while a third mutant required only cocultivation with H9 cells. Sequencing of cDNA from cells infected with this last mutant demonstrated that the parental mutant sequence was retained and that genotypic revertants to the wild-type as well as new mutant sequences were generated. These results suggest that tat-defective HIV-1 provirus can be activated by UV and can subsequently revert to wild-type virus. This study raises the possibility that UV exposure of immune cells in the skin plays a role in the activation of defective HIV-1 in vivo.
Sadaie
M R
MR
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Tschachler
E
E
Valerie
K
K
Rosenberg
M
M
Felber
B K
BK
Pavlakis
G N
GN
Klotman
M E
ME
Wong-Staal
F
F
D000163:Acquired Immunodeficiency Syndrome / Q000209:etiology* / Q000473:pathology; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology* / Q000528:radiation effects / Q000648:ultrastructure; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000737:chemistry; D005455:Fluorescent Antibody Technique; D015696:Gene Products, tat / Q000096:biosynthesis / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development* / Q000528:radiation effects; D006367:HeLa Cells / Q000382:microbiology / Q000648:ultrastructure; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011533:Proviruses / Q000235:genetics / Q000254:growth & development / Q000528:radiation effects; D014407:Tumor Cells, Cultured; D014775:Virus Activation / Q000235:genetics; D054322:tat Gene Products, Human Immunodeficiency Virus
D004279:DNA, Viral; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus