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
"An important unresolved issue of AIDS pathogenesis is the mechanism of human immunodeficiency virus (HIV)-induced CD4 (+) T-lymphocyte destruction," according to Michael J. Lenardo and colleagues working at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, and George Washington University in Washington, DC.
While env is able to hasten HIV-induced necrotic cell death, it is does not play a crucial role in this process, Lenardo and coauthors found.
They exposed T cells to HIV strains pseudotyped with vesicular stomatitis virus glycoprotein to remove the rate-limiting effect of the HIV envelope on infection. Although viral strains with intact env regions induced significantly more rapid cell death than their env (-) counterparts, env expression was not necessary for necrosis, study data showed.
The addition of HIV protease inhibitors to env (+) cultures prevented the gene from enhancing viral cytopathicity. Since protease inhibitors block newly produced viral particles from maturing into infectious viruses, this finding suggests that the effects of env are mediated by new viruses reinfecting afflicted cells, according to the report.
Moreover, cytopathicity was comparable between nef (+) and nef (-) HIV constructs although replacing all viral protein-coding sequences with green fluorescent protein did prevent HIV-induced necrosis (Cytopathic killing of peripheral blood CD4 (+) T lymphocytes by human immunodeficiency virus type 1 appears necrotic rather than apoptotic and does not require env, J Virol 2002 May;76(10):5082-93.
"Thus, env can accelerate cell death chiefly as an entry function, but one or more viral functions other than env or nef is essential for necrosis of CD4 (+) T cells induced by HIV-1," Lenardo and colleagues concluded.
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, Room. 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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