Virus-Induced Immunosuppression Is Linked to Rapidly Fatal Disease in Infant Rhesus Macaques Infected with Simian Immunodeficiency Virus

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Abstract
Six newborn rhesus macaques were experimentally infected with pathogenic Simian immunodeficiency virus of macaques (SIVmac251), and three newborn macaques were infected with avirulent SIVmac1A11. The former developed rapidly fatal simian AIDS and died within 26 wk of age, whereas the latter remained clinically normal. Infant monkeys that developed rapidly progressive disease had rapid declines in CD4+ cells and were unable to mount IgG and IgA antibody responses to SIV or to an unrelated antigen, tetanus toxoid. IgM antibody responses were near normal to both SIV-specific and nonspecific antigens. Cytotoxic T lymphocyte (CTL) responses to SIV envelope were observed in animals infected with either virulent or avirulent SIV. These studies demonstrated that virulent SIVmac infection induced a rapid immunosuppression that was both SIV-specific and nonspecific in nature. The observation that virulent strains of SIV can rapidly induce a global immunosuppression provides one explanation for the rapid disease course in some HIV-infected children and supports the strategy of early and vigorous antiviral drug therapy to alter the disease course even if this does not prevent infection.