Nef-mediated downregulation of CD4 enhances human immunodeficiency virus type 1 replication in primary T lymphocytes

Journal of Virology
Christopher A LundquistC Aiken

Abstract

The accessory protein Nef plays a crucial role in primate lentivirus pathogenesis. Nef enhances human immunodeficiency virus type 1 (HIV-1) infectivity in culture and stimulates viral replication in primary T cells. In this study, we investigated the relationship between HIV-1 replication efficiency in CD4(+) T cells purified from human blood and two various known activities of Nef, CD4 downregulation and single-cycle infectivity enhancement. Using a battery of reporter viruses containing point mutations in nef, we observed a strong genetic correlation between CD4 downregulation by Nef during acute HIV-1 infection of activated T cells and HIV-1 replication efficiency in T cells. In contrast, HIV-1 replication ability was not significantly correlated with the ability of Nef to enhance single-cycle virion infectivity, as determined by using viruses produced in cells lacking CD4. These results demonstrate that CD4 downregulation by Nef plays a crucial role in HIV-1 replication in activated T cells and underscore the potential for the development of therapies targeting this conserved activity of Nef.

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Citations

Dec 14, 2011·Plant Cell Reports·Sergio Rosales-MendozaLeticia Moreno-Fierros
Aug 11, 2005·Current HIV/AIDS Reports·Jenny L Anderson, Thomas J Hope
Sep 19, 2003·Current Infectious Disease Reports·Jenny L. Anderson, Thomas J. Hope
Aug 19, 2010·AIDS Research and Human Retroviruses·Annette AudigéUNKNOWN Swiss HIV Cohort Study (SHCS)
May 13, 2004·Journal of Virology·Luciana J CostaB Matija Peterlin
Aug 28, 2004·Journal of Virology·G Grant WelsteadChristopher D Richardson
Sep 18, 2013·Retrovirology·Jaclyn K MannZabrina L Brumme
Nov 1, 2013·Retrovirology·Richard L WatkinsJ Victor Garcia
Jul 27, 2007·Retrovirology·Juan Lama, Vicente Planelles
Sep 24, 2008·Retrovirology·John L Foster, J Victor Garcia
Apr 11, 2009·Retrovirology·Jan SchmökelFrank Kirchhoff
Jul 28, 2010·AIDS Research and Therapy·Yong-Jiu JinSteven J Burakoff
Feb 2, 2013·PloS One·Mohamed El-FarRafick-Pierre Sékaly
Dec 14, 2011·Viruses·Christopher J A Duncan, Quentin J Sattentau
Oct 15, 2013·AIDS Research and Human Retroviruses·Maria SalgadoJoel N Blankson
Apr 6, 2013·Immunotherapy·Sharon Lam, Catherine Bollard
Sep 17, 2004·Proceedings of the National Academy of Sciences of the United States of America·Allison OlszewskiGregory A Weiss

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