3rd Conference on Retroviruses and Opportunistic Infections Washington, DC - January 28-February 1, 1996

Conf Retroviruses Opportunistic Infect 1996 Jan 28-Feb 1; 3rd:59 (abstract no. 34)

Strizki JM, Albright AV, O'Connor M, Gonzalez-Scarano F
University of Pennyslvania, Philadelphia, PA.

Many HIV-l infected individuals develop symptoms of neurological dysfunction collectively termed the AIDS Dementia Complex (ADC). The cellular and virological factors responsible for the neuroinvasion and neuropathogenesis of HIV are poorly understood, although histopathological and clincial evidence suggests that virus is present in the brain at all stages of infection, and that microglia are the predominant cell type infected. To ascertain whether viruses present at the time of primary viremia can infect the CNS, and to determine if microglial tropism is distinct from MDM-tropism, twenty-two HIV-1 isolates obtained from acutely infected individuals were assayed for their ability to replicate in primary adult microglial cultures and MDM. While most isolates displayed parallel tropism, several isolates replicated preferentially in one of the two cell types, differing by as much as 1000 fold in p24 production. This suggested that MDM and microglial tropism overlap but that some isolates can exhibit somewhat discrete phenotypes. One acute isolate was further adapted to microglia by 14 sequential passages, at which, point it exhibited a 100-1000 fold increase in p24 production when compared with the original unpassaged virus stock. In addition, the passaged virus exhibited increased and marked cytopathology (vacuolization and syncytia formation) in infected microglial cultures. Sequence comparison of the V3 loop of unpassaged and multiply passaged virus did not reveal any significant changes, suggesting that regions other than V3 may be important for infection of microglia. Taken together our data support the hypothesis that HIV-l infection can be established in the CNS by viruses present early in HIV infection, and that once established, adaptation can result in the selection of a pool of predominantly neurotropic viruses. Current efforts are directed at obtaining molecular clones of microglia-tropic isolates, and elucidation of the viral elements responsible HIV neurotropism.

960128
34

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