  
Nef protein facilitates cytoplasmic entry of HIV
Last Updated: 2001-04-13 11:32:00 EDT (Reuters Health)
WESTPORT, CT (Reuters Health) - Contrary to findings from previous studies, the Nef protein of HIV-1 appears to promote cytoplasmic entry of the virus during plasma membrane fusion.
Dr. Evelyne Schaeffer, from the Gladstone Institute of Virology and Immunology in San Francisco, and colleagues used epifluorescence microscopy to monitor the entry of a green fluorescent protein-Vpr-labeled HIV virion into HeLa cells expressing or not expressing CD4+. The researchers also assessed the infectivity of HIV-1 virions containing intact or mutated forms of Nef.
The researchers found that endocytosis was a very active pathway for virus uptake, confirming the findings of earlier studies. However, this mechanism of virus uptake did not seem to produce a productive infection in the host cell, according to their report in the March issue of the Journal of Virology.
CD4+ and chemokine receptor-dependent entry of HIV virions into the target cell's cytoplasm were significantly enhanced in the presence of HIV Nef, the authors state. Mutations in Nef that impaired its ability to downregulate CD4+ or disrupted its polyproline helix reduced its ability to promote cytoplasmic virion entry.
"In previous studies, these effects of Nef at the level of cellular entry were likely masked by a high background of virion entry by endocytosis that was not altered by Nef," the investigators explain.
"Our findings raise the possibility that the previously described effects of Nef on proviral DNA synthesis likely results from an earlier action at the level of viral entry," they state. "Additional effects of Nef on proviral DNA synthesis cannot be completely excluded, yet the recognition that HIV-1 Nef functions as an entry factor provides new insights into the molecular basis of its function as an accelerator of HIV-1 pathogenesis."
J Virol 2001;75:2993-3001.
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