Cellular Immune Response of Rhesus Monkeys Infected with a Partially Attenuated nef Deletion Mutant of the Simian Immunodeficiency Virus

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To date the vaccines most successful in the simian immunodeficiency virus (SIV) model of AIDS are live attenuated viruses. However, the virus-specific immune response induced after infection of monkeys with attenuated SIV has not been described comprehensively. Therefore, we investigated the cellular immune response of eight rhesus macaques infected with a nef deletion mutant of SIVmac32H (pC8). In contrast to monkeys infected with pathogenic SIV, pC8-infected macaques developed a virus-specific T-cell proliferation. In addition, all animals showed a proliferative T-cell response to recall antigen and mitogens. In six of eight monkeys virus-specific cytotoxic T-cells directed against different SIV polypeptides were detected. In two animals, however, the truncated nef gene reverted to full length 12 weeks after pC8 infection. These two monkeys developed hematological alterations, indicating an immunodeficiency. Simultaneously with the onset of disease the animals lost their T-cell responsiveness against recall antigens. Eight weeks later their T-cell reactivity against mitogens was also abrogated. The results indicate that live attenuated SIV induced a virus-specific cellular immune response in monkeys which might be associated with the previously reported resistance to superinfection with pathogenic SIV. Paradoxically, if the attenuated SIV reverts in vivo to a more virulent virus, the SIV-specific immune response was inefficient to prevent the onset of immunodeficiency in the animals.