Neuropathologic aspects of lentiviral infections.
Studies of lentiviral infections of various animals and man have shown that all may invade the CNS and induce pathological lesions. This is well established in infections with VV, CAEV, SIV, HIV-1, and FIV. Although VV and CAEV do not cause an overt immunodeficiency, they share several features pertinent for the establishment of neuropathologic lesions with those that induce immunodeficiency. This holds especially true for the initial steps and early CNS lesions. 1) Infection of the CNS is from the blood stream. Although a definite proof of how the different viruses cross the blood-brain barrier remains to be brought forward there are indications that it may occur through migration of infected monocytes and/or lymphocytes into the brain. Furthermore free virus may enter the CNS, either directly or through infection of endothelial cells. 2) The lesion pattern at least in initial stages is similar; that is, it consists of meningitis, perivascular infiltrations especially of the deep white matter, and inflammation of the choroid plexus. In visna a local amplification of the inflammatory response is frequently observed in choroid plexus often with formation of active lymphoid follicles. Multinucleated giant cells are prominent in HIV-1 and SIV infections, but rare in VV, and practically nonexistent in infections with FIV and CAEV, possibly a reflection of differences in virus replication. Myelin breakdown is a feature of various lentiviral infections but its mechanisms and morphological expression may vary. Sharply demarcated plaques of primary demyelination seem to be unique for VV infection and vacuolar myelopathy for infection with HIV-1. 3) The main target cells in the brain are cells of the monocyte/macrophage/microglial lineage. In visna infected monocytes are found but evidence for infection of the enigmatic resident microglial cells is still lacking. Infection, especially productive, of neuroectodermal cells is rare, but may, however be important for viral persistence. Infection of endothelial cells occurs in the various lentiviral infections and may play a part in viral entry into the CNS and contribute to tissue damage. 4) The discrepancy between the frequency of productively infected cells and cell types infected and extent and character of pathological lesions, indicates that a mechanism other than the direct effect of the virus contributes to the evolution of CNS lesions. In HIV-1 infection evidence, mainly obtained by in vitro studies, indicates that lesions are mediated by cytokines and other toxic factors secreted by inflammatory or glial cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Institute for Experimental Pathology, University of Iceland, Keldur v/Vesturlandsveg, Reykjavík.
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D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology / Q000473:pathology; D000818:Animals; D001812:Blood-Brain Barrier; D002493:Central Nervous System Diseases / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D016086:Lentivirus / Q000502:physiology; D016180:Lentivirus Infections / Q000382:microbiology / Q000473:pathology*; D014766:Viremia