Infectivity and pathogenesis of titered dosages of simian immunodeficiency virus experimentally inoculated into longtailed macaques (Macaca fascicularis).

The 50% macaque infectious dose (MID50) and pathogenesis of uncloned simian immunodeficiency virus (isolated from a pigtailed macaque, SIVmne) was determined in longtailed macaques (Macaca fascicularis). Five pairs of macaques were inoculated with 10-fold dilutions of the virus stock, and one macaque was mock-infected. The virologic and clinical status of these macaques was monitored for up to 80 weeks. The MID50 of SIVmne was determined to be 10(2) cell culture infectious dose of the original virus stock. In order to test the infectivity and pathogenesis of an established viral dose, six additional macaques were inoculated with 10x MID50 (10(3) cell culture infectious dose) of the SIVmne. The virologic and clinical status of these macaques was monitored for 40 weeks. All of the macaques inoculated with 10x MID50 or greater became infected as evidenced by seroconversion and consistent virus isolation from peripheral blood mononuclear cells. Macaques infected with SIVmne had an initial sharp decrease in CD2, CD20, CD4, CD8, and CD4CD29 lymphocyte subsets, whereas the CD4:CD8 ratio increased. Viremic macaques developed persistent slight to moderate peripheral lymphadenopathy approximately 3 to 4 weeks after inoculation. Four macaques subsequently died of AIDS-like disease at 29, 33, 42, and 80 weeks after inoculation. Data obtained from the viral titration study and the acute infection model will aid in the development of animal trials to evaluate antiretroviral therapies and preventive vaccines against human immunodeficiency virus infection.