Important note: Information in this article was accurate in June 2002. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; June 17, 2002
Michael Greer, Senior Medical Writer
"A better understanding of the death process occurring in infected cells may provide valuable insight into the viral component responsible for cytopathicity," argued Dr. Diane L. Bolton and colleagues working at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland. "This would aid the design of preventive treatments against the rapid decline of CD4 (+) T cells that results in AIDS."
Although the exact mechanisms of CD4 cell death remain unclear, Bolton and coauthors made a surprising discovery - contrary to conventional wisdom, these cells are not susceptible to HIV-induced apoptosis.
The researchers assessed the results of exposing Jurkat and H9 CD4 (+) T cells to HIV in vitro. Previous studies had implicated apoptotic processes in the inevitable death of these cells, they said.
However, none of the characteristic signs of apoptosis were seen after infection. Caspase activity was marginal or absent, as was TUNEL signaling and annexin V or APO2.7 expression, study data showed.
Cells deficient in proapoptosis proteins, or treated with antiapoptotic agents, were just as vulnerable to HIV as their wild-type counterparts (Death of CD4 (+) T-cell lines caused by human immunodeficiency virus type 1 does not depend on caspases or apoptosis, J Virol 2002 May;76(10):5094-107.
"These results suggest that the primary mode of cytopathicity by laboratory-adapted molecular clones of HIV-1 in cultured cell lines is not via apoptosis," Bolton and colleagues concluded. "Rather, cell death occurs most likely via a necrotic or lytic form of death independent of caspase activation in directly infected cells."
The corresponding author for this report is Michael J. Lenardo, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bldg. 10, Rm. 11N311, 10 Center Dr., MSC 1892, Bethesda, MD 20892 USA. E-mail: lenardo@nih.gov.
Key points reported in this study include:
This article was prepared by AIDS Weekly editors from staff and other reports.
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