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AIDS and HIV Pathogenesis: HIV Nef protein protects infected cells from apoptosis <p></b>
Michael Greer, Senior Medical Writer
March 11, 2002
-- The HIV Nef protein helps to prolong the lives of infected cells, researchers in Australia report.

"The nef gene product of human immunodeficiency virus type 1 (HIV-1) is important for the induction of AIDS, and key to its function is its ability to manipulate T-cell function by targeting cellular signal transduction proteins," explained Dr. Alison L. Greenway and colleagues at the National Centre in HIV Virology Research in Fairfield, the Peter MacCallum Cancer Institute in East Melbourne, and the Biomolecular Research Institute in Parkville.

One such protein inhibited by Nef is involved in inducing apoptosis in HIV infected cells, Greenway and coauthors found.

The researchers found that part of the HIV Nef protein contains the binding domain for p53, a tumor suppressor protein. Nef-p53 interactions were observed in culture models of HIV infection, they said.

Nef blocked p53-mediated apoptosis in the human MOLT-4 leukemic T-cell line, study data showed. The 57-residue Nef fragment containing the p53-binding domain prevented apoptosis just as well as the complete protein.

Nef appeared to act by lowering the half-life of p53, which reduces in turn the tumor suppressor's functional ability (Human immunodeficiency virus type 1 Nef binds to tumor suppressor p53 and protects cells against p53-mediated apoptosis, J Virol 2002 Mar;76(6):2692-702.

"These data show that HIV-1 Nef may augment HIV replication by prolonging the viability of infected cells by blocking p53-mediated apoptosis," Greenway and colleagues concluded.

The corresponding author for this report is Alison L. Greenway, PhD, AIDS Cellular Biology Unit, Macfarlane Burnet Centre for Medical Research, Yarra Bend Rd., Fairfield, Victoria 3078, Australia. E-mail: greenway@burnet.edu.au.

Key points reported in this study include:

  • The HIV Nef protein helps prevent apoptosis in HIV infected cells

  • It does so by inhibiting the activity of the tumor suppressor protein p53

  • p53 is a potent inducer of apoptosis in damaged or infected cells

This article was prepared by AIDS Weekly editors from staff and other reports.



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