"Expression Directed From HIV Long Terminal Repeats in the Central Nervous" System of Transgenic Mice

Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.

"Expression Directed From HIV Long Terminal Repeats in the Central Nervous" System of Transgenic Mice

Science (12/11/92) Vol. 258, No. 5089, P. 1804
Corboy, John R. et al.

Abstract: Differences in the nucleotide sequence of the long terminal repeats (LTRs) of different HIV strains can alter the tissue-specific pattern of gene expression directed from their LTRs, as has been observed for other retroviruses, write John R. Corboy et al. of the Johns Hopkins University School of Medicine in Baltimore, Md. Infection with HIV is often accompanied by the AIDS dementia complex (ADC). The researchers constructed transgenic mice that contained the 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. The findings are unexpected because HIV-1 replication in the CNS has not been detected in neurons. But the pathogenesis of the neuronal cell loss seen in ADC is still uncertain. In autopsy studies of the brains of individuals with ADC, macrophages and microglia are the cells most commonly infected with HIV-1. Infrequently in autopsy and biopsy studies, other CNS cells, including endothelial cells, astrocytes, and oligodendrogli and neurons are found to be infected. In tissues other than those of the CNS, HIV-1 primarily infects T lymphocytes and macrophages that express the surface molecule CD4. But CD4 may not be necessary for HIV-1 infection of neural-derived primary or cultured cells, where the virus may use other molecules for entry into cells. If these CNS-derived strains are able to enter into the cell, neurons can produce cellular transcription factors that interact with and direct expression from LTRs, the researchers conclude.

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