This project is designed to study the acute events of viral infection and dissemination of HIV-2287 throughout tissues in pigtailed macaques following infection by either intravenous or mucosal (intravaginal or intrarectal) routes. One animal is sham-inoculated with tissue culture media with each group as a control. Experimental animals are euthanatized at several time points post-inoculation (PI). Tissues are harvested at necropsy for analysis of viral infection and histopathology by PCR, in situ hybridization, and special staining techniques. The macaques that were inoculated intravenously received 50 TCID50, a dose calculated to produce 100% infection in all the animals. These animals showed a detectable infection in lymphoid tissues by all assays beginning at day 4 PI, with a dramatic peak in viral infection, correlating with a loss of circulating CD4+ lymphocytes, at days 10-14 PI. The later time points showed a decline in the number of infected cells in tissue s an d circulating lymphocytes. The animals that were inoculated intrarectally received 1000 TCID50 HIV-2287. This dose has previously been shown to produce 100% infection in the macaques. This part of the study is still underway and results are pending. FUNDING NIH grant RR00166. Eitner, F., Cui, Y., Hudkins, K.L., Anderson, D.M., Schmidt, A., Morton, W.R., and Alpers, C.E. Chemokine receptor (CCR5) expression in human kidneys and in the HIV infected macaque. Kidney Int. 54:1945-54, 1998.
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