Evidence of productively infected CD8+ T cells in patients with AIDS: implications for HIV-1 pathogenesis.
CD8+ T lymphocytes play an important protective role against HIV infection. The onset of AIDS is associated with a decline in both the number of CD8+ T lymphocytes and anti-HIV cytotoxic activity in CD8+ T cells. The reason for this progressive failure of CD8+ T cells in HIV-1 infection remains unknown. Earlier reports have shown presence of viral DNA in CD8+ cells of HIV-1-infected patients; under some conditions, CD8+ T cells have been shown to express CD4 in vitro and can be susceptible to infection with HIV-1. However, whether CD8+ lymphocytes in vivo can be productively infected with HIV-1 remains unclear. In this study, we generated multiple CD8+ T-cell clones from two patients with AIDS. These clones were CD8+/CD3+ but did not express CD4. Several of these CD8+ clones from both patients were found to be endogenously infected with HIV-1 and spontaneously produced these viruses. CD8+ cell-produced HIV-1 was biologically competent because viruses produced by most of these clones could efficiently infect and replicate in peripheral blood lymphocytes from HIV-negative donors. In addition, some of these viruses were able to form syncytia in MT-2 cells indicating syncytium-inducing phenotype. Comparison of the sequences in V3 loop areas among different viruses showed changes in some of the clones from both patients. For the first time, this report provides direct evidence that mature CD8+ T cells can be productively infected with HIV-1 in patients with AIDS. Direct infection of CD8+ T lymphocytes may play a role in the eventual failure of these cells in HIV-1 infection.
Children's Research Institute, Department of Pediatrics and Molecular Virology, Immunology, & Medical Genetics, The Ohio State University Medical Center, Columbus, Ohio 43205-2696, USA. sahak@pediatrics.ohio-state.edu
K
K
Saha
J
J
Zhang
B
B
Zerhouni
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000821:virology*; D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000821:virology*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002999:Clone Cells; D004279:DNA, Viral / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D017422:Sequence Analysis, DNA; D014779:Virus Replication
D015704:CD4 Antigens; D016827:CD8 Antigens; D004279:DNA, Viral; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments