HIV-INFECTION OF MACROPHAGES AND PATHOGENESIS OF AIDS DEMENTIA COMPLEX - INTERACTION OF THE HOST-CELL AND VIRAL GENOTYPE

AIDS dementia complex (ADC) develops in only a third of HIV-infected p atients who progress to AIDS, Macrophages and microglial cells are the major cellular sites of productive HIV replication in brain, Using 11 blood isolates of HIV from asymptomatic patients there was marked var iation in tropism and the level of productive infection in recently ad herent monocytes and monocyte-derived macrophages cultured in vitro, H owever, less variation was seen with 19 blood isolates from advanced H IV infection and 11 postmortem tissue isolates from brain, cerebrospin al fluid, spleen, and lung, Newly adherent monocytes expressed CCR5 in all seven patients tested, consistent with their susceptibility to in fection but not explaining the above variability, There is also marked regional variability in neuropathology in the brain of patients with ADC, We have demonstrated that there was marked variation in the V3 se quences of HIV clones from different regions of the cortex of a patien t with ADC, suggesting independent evolution of HIV replication in bra in, Furthermore, production of the neurotoxin quinolinic acid from HIV -infected macrophages varied, depending on the host and source of HIV isolate, Hence variations in viral genotype, production by infected ma crophages, and subsequent toxin production may contribute to the varia bility in neuropathology between individuals and between different reg ions of the brain in the same individual.