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. 35)

Kolson DL, Llanes CE, Kim FM, Collman RG
University of Pennsylvania. Philadelphia, PA.

The NTera-2 human cell line is a neuronally-committed cell which, upon exposure to retinoic acid, differentiates into a post-mitotic phenotype with features of mature neurons. NTera-2 cells grow in large numbers as greater than 99% pure neurons, and we are utilizing them to study direct and indirect effects of HIV-1 on both neuronal function and survival relevant to the pathogenesis of AIDS Dementia Complex (ADC). First, we found that NTera 2 neurons express relevant neuronal functions that are potential targets for HIV-1 -induced dysfunction even without induction of cell death. These include high-affinity transport of glutamate and GABA (gamma-aminobutyric acid), and expression of multiple molecular forms of the neurotransmitter enzyme acetylcholinesterase (AChE) that resemble those in developing CNS neurons. Second, NTera 2 cells are susceptible to restricted infection by a limited number of HIV-1 strains (see abstract by Yi et al). Third, we have developed a multi-cell co-culture model in which NTera-2 cells are maintained with primary human monocyte-derived macrophages (MDM) and primary astrocytes derived from rat brain. In this mixed cell model the MDM remain susceptible to productive infection with microphage-tropic strains of HIV-1, and differentiated human neurons can be cultured in contact with infected macrophages and astrocytes, reflecting cell-cell interactions in the brain believed to be critical to development of neuronal dysfunction in ADC. Thus, the NTera-2 neuronal cell line and our multi-component cell co-culture system will be a valuable model with which to examine functional and toxic effects resulting from HIV-1 infection of microphage cells and direct or indirect mechanisms involving neurons and other glial cells.

960128
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