SCID MICE WITH HIV ENCEPHALITIS DEVELOP BEHAVIORAL ABNORMALITIES

Severe combined immunodeficient (SCID) mice inoculated intracerebrally (IC) with HIV-infected human monocytes develop brain pathology simila r to that in humans with HIV encephalitis. This includes HIV-positive macrophages and multinucleated giant cells, astrogliosis, microglial n odules, and neuronal dropout. These xenografts survive about 1 month. To develop a model of chronic HIV encephalitis and to assay the result ing behavioral abnormalities, we reinoculated SCID mice IC every 4 wee ks for 3 months with either HIV-infected human monocytes (n = 5) or un infected human macrophages (n = 4) or administered no inoculation (n = 6); these three groups were monitored for behavioral abnormalities. T ests of cognitive function in a Morris water maze 3.5 months after the first inoculation suggested that HN-infected mice performed poorly co mpared with controls. Following testing in the water maze on days 4 an d 5 of acquisition, motor activity of infected mice was reduced in com parison with that of controls. Retention of goal location when tested 1 week later was impaired in HIV-infected mice compared with controls. Histopathologic analysis of brains revealed significant astrogliosis and strongly suggested higher numbers of major histocompatibility comp lex (MHC) class II-positive multinucleated macrophages in HIV-infected compared with control mice. Thus, our preliminary studies indicate th at SCID mice with HIV encephalitis develop behavioral abnormalities re miniscent of human disease. These behavioral abnormalities are associa ted with significantly increased astrogliosis, the presence of HIV, an d probably multinucleated giant cells. These studies further support t he use of this SCID animal model system for studies of the pathogenesi s of HIV encephalitis and for drug interventions.