ABSTRACT
A large stock preparation of the HIV-1SF2 isolate has been derived after serial passage in human peripheral blood mononuclear cells (PBMCs). This viral stock has a titer of 10(4.9) TCID50 in human PBMCs and 10(4.2) TCID50 in chimpanzee PBMCs. By inoculation into animals the 50% chimpanzee infectious dose titer was found to be about 10(2.3). Virus isolation from animals was achieved on most occasions within 1-4 weeks after inoculation and then became transient. Viral RNA and DNA PCR analyses confirmed the virus infection of the chimpanzees. Anti-HIV antibody levels in the inoculated animals ranged from 1:400 to 1:6400 as measured by ELISA. About 680 vials of this stock preparation, frozen at -190 degrees C, are available for future studies of vaccines and antiviral therapies.
Subject(s)
AIDS Vaccines , HIV-1 , Animals , DNA, Viral/chemistry , Enzyme-Linked Immunosorbent Assay , HIV-1/pathogenicity , Humans , Pan troglodytes , Polymerase Chain Reaction , RNA, Viral/chemistryABSTRACT
The mechanism by which CD8+ T cells from human immunodeficiency virus (HIV)-infected individuals suppress HIV replication in acutely infected CD4+ T cells was investigated. Cytotoxicity was not involved, as the antiviral activity of the CD8+ cells did not correlate with the ability to lyse HIV-infected or uninfected CD4+ T cells. In addition, the frequency of HIV-infected CD4+ cells increased during coculture with CD8+ T cells even in the absence of detectable levels of virus replication. Moreover, separation of the CD4+ and CD8+ cells by a 0.4-micron-pore-size filter delayed HIV replication, indicating a role, at least in part, for a soluble factor. However, cell contact was required for optimal antiviral activity. These results extend further the observation on the mechanism of antiviral HIV activity by CD8+ cells from infected individuals. They support the conclusion that CD8+ cells can play a major role in preventing development of disease in HIV-infected individuals.
Subject(s)
CD4 Antigens/immunology , CD8 Antigens/immunology , HIV Seropositivity , HIV/physiology , T-Lymphocyte Subsets/immunology , Virus Replication , Antibodies, Monoclonal , Antigens, CD/analysis , Cells, Cultured , Cytotoxicity, Immunologic , HIV/immunology , Humans , Lymphocyte Activation , Time FactorsABSTRACT
T lymphocytes expressing the CD8 surface antigen block HIV replication in CD4+ peripheral blood cells from HIV-infected individuals. We report here that CD4+ cells from HIV seronegative donors, when infected in vitro with HIV, also do not replicate virus when cocultured with CD8+ T cells from HIV-infected individuals. CD8+ cells from HIV-uninfected donors did not show this effect on virus replication. HLA-restriction of the antiviral response was not observed, and virus-containing cells were not eliminated from culture. The antiviral activity was broadly cross-reactive, as CD8+ cells from individuals infected only with HIV-1 suppressed the replication of diverse strains of HIV-1 and HIV-2, as well as the simian immunodeficiency virus. This ability of CD8+ cells to control HIV replication could play an important role in the maintenance of an asymptomatic state in HIV-infected individuals.
