6th International AIDS Conference


San Francisco, California, USA — June 20-23, 1990

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The neuropathogenic potential of HIV-1 isolates in CNS organotypic cultures.

Int Conf AIDS 1990 Jun 20-23; 6:337 (abstract no. 1095)
Lyman WD, Hatch WC, Tricoche M, Kress Y, Chiu FC, Rashbaum WK, Soeiro R; Albert Einstein College of Medicine, Bronx, NY, USA

OBJECTIVE: The human immunodeficiency virus type-1 (HIV-1) can be detected in the central nervous system (CNS) of patients with the acquired immunodeficiency syndrome (AIDS). The association of HIV-1 with CNS lesions has led to the belief that HIV-1 is neurotropic and neurovirulent. However, the precise role of HIV-1 in CNS pathology remains enigmatic. The enigma is compounded by the fact that different isolates of HIV-1 may have distinct cellular tropisms. This study compares the potential of various HIV-1 isolates to cause pathologic changes in human fetal CNS organotypic cultures.

METHODS: Explants of human fetal CNS are maintained in organotypic culture for up to 8 weeks. Initial studies, using light and electron microscopy (LM and EM) in combination with immunocytochemistry and Western blots, confirm that the cultures contain normal nervous tissue cellular elements. After obtaining baseline values, cultures are exposed to various HIV-1 isolates including IIIB, IIIcc, RF, MN (obtained from peripheral blood cells) or BR, JR-CSF, JR-FL, and SF162 (obtained from CNS tissue or cerebrospinal fluid of AIDS patients). The resultant infection and pathology are analyzed using protein chemistry, immunocytochemistry in combination with LM and EM, and by application of the polymerase chain reaction.

RESULTS: There is no significant difference in the ability of the various HIV-1 isolates tested to cause significant pathologic changes in CNS tissue. The pathology associated with each isolate consists of extracellular edema, intracytoplasmic lipid deposition, dissolution of normal chromatin patterns and cellular drop-out.

CONCLUSIONS: Because different HIV-1 isolates cause equivalent CNS pathology in vitro, variations in AIDS neuropathology in vivo may not be related to proposed differences in the neural cell tropisms of distinct isolates but rather to other factors.

Keywords: AEGIS, HIV-1, Central Nervous System, Acquired Immunodeficiency Syndrome, Culture, Microscopy, Electron, Human, In Vitro, ICA6KWDaegis,hiv-1,centralnervoussystem,acquiredimmunodeficiencysyndrome,culture,microscopy,electron,human,invitro,ica6

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