Potential Relationships Between the Presence of HIV, Macrophages, and Astrogliosis in SCID Mice with HIV Encephalitis

Abstract

The pathogenesis of HIV encephalitis (HIVE) has not been determined although increased numbers of mononuclear phagocytes (macrophages and microglia), some of which are HIV-infected, and reactive astrogliosis are important pathological findings in this condition. For this experiment, fifty-one SCID mice were inoculated intracerebrally either with human cells and HIV-1, human cells only or HIV only and then sacrificed at various time points. HIV gag mRNA was detected by reverse transcriptase polymerase chain reaction (PCR) distant from the site of inoculation in 73% of mouse brains inoculated with HIV and human cells attesting to the pervasiveness of HIV infection in SCID brain. HIV mRNA was detected as long as 91 days after inoculation of human cells and virus and the presence of HIV gag, nef, and tat/rev mRNA in HIV-infected SCID brains indicates ongoing HIV mRNA synthesis. Brain tissue sections were immunostained for HIV, human macrophages, and astrocytes from a subset of mice (n = 29) from the above groups and qualitatively assessed. PCR data for HIV mRNA was correlated with staining results and these data suggested that the greatest astrogliosis was present in mice inoculated with HIV and human cells, consistent with previously reported data. The data further suggest that astrogliosis is greater when HIV is detected. Taken together the data are consistent with a synergistic effect between macrophages and HIV in the development of astrogliosis.