Infection with the human immunodeficiency virus (HIV) is frequently accompanied by the AIDS (acquired immunodeficiency syndrome) dementia complex. The role of specific HIV genetic elements in the pathogenesis of central nervous system (CNS) disease is not clear. Transgenic mice were constructed that contained the long terminal repeats (LTRs) of two CNS-derived strains and a T cell tropic strain of HIV-1. Only mice generated with CNS-derived LTRs directed expression in the CNS, particularly in neurons. Thus, some strains of HIV-1 have a selective advantage for gene expression in the brain, and neurons can supply the cellular factors necessary for their transcription.
The simian immunodeficiency virus, SIVmac, causes disease affecting multiple organ systems in macaques similar to human immunodeficiency virus infection in humans. Molecularly cloned SIVmac with a strong lymphocyte tropism was used in pathogenesis experiments to correlate viral cell tropism with disease. In 5 animals, exhaustive analyses on viruses from tissues and identification of infected precursor cells were done at multiple times during infection to ensure the virus had not mutated into a macrophage-tropic variant. Viral replication was measured by infectivity, infectious center assays, and in situ hybridization. Lymphocytes produced most virus in tissues, indicating the virus maintained its cell tropism in vivo. Lymphocytes in bone marrow were latently infected and those in the spleen and lymph nodes were productively infected. The virus failed to replicate in the brain after intracerebral inoculation. SIVmac that maintained a strong tropism for lymphocytes and a corresponding poor tropism for macrophages can cause persistent infection and AIDS but not other diseases such as primary pneumonia and encephalitis in rhesus macaques.
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