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Journal of Virology, November 2008, p. 10811-10819, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01150-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Nef Can Enhance the Infectivity of Receptor-Pseudotyped Human Immunodeficiency Virus Type 1 Particles{triangledown}

Massimo Pizzato,1 Elena Popova,2 and Heinrich G. Göttlinger2*

Department of Infectious Diseases, Division of Medicine, Imperial College London, London W2 1PG, United Kingdom,1 Program in Gene Function and Expression, Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 016052

Received 2 June 2008/ Accepted 14 August 2008

Nef is an accessory protein of human immunodeficiency virus type 1 (HIV-1) that enhances the infectivity of progeny virions when expressed in virus-producing cells. The requirement for Nef for optimal infectivity is, at least in part, determined by the envelope (Env) glycoprotein, because it can be eliminated by pseudotyping HIV-1 particles with pH-dependent Env proteins. To investigate the role of Env in the function of Nef, we have examined the effect of Nef on the infectivity of Env-deficient HIV-1 particles pseudotyped with viral receptors for cells expressing cognate Env proteins. We found that Nef significantly enhances the infectivity of CD4-chemokine receptor pseudotypes for cells expressing HIV-1 Env. Nef also increased the infectivity of HIV-1 particles pseudotyped with Tva, the receptor for subgroup A Rous sarcoma virus (RSV-A), even though Nef had no effect if the pH-dependent Env protein of RSV-A was used for pseudotyping. However, Nef does not always enhance viral infectivity if the normal orientation of the Env-receptor interaction is reversed, because the entry of Env-deficient HIV-1 into cells expressing the vesicular stomatitis virus G protein was unaffected by Nef. Together, our results demonstrate that the presence of a viral Env protein during virus production is not required for the ability of Nef to increase viral infectivity. Furthermore, since the infectivity of Tva pseudotypes was blocked by inhibitors of endosomal acidification, we conclude that low-pH-dependent entry does not always bypass the requirement for Nef.

* Corresponding author. Mailing address: UMass Medical School, LRB 526, 364 Plantation Street, Worcester, MA 01605. Phone: (508) 856-2843. Fax: (508) 856-4650. E-mail: heinrich.gottlinger{at}umassmed.edu

{triangledown} Published ahead of print on 20 August 2008.

Journal of Virology, November 2008, p. 10811-10819, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01150-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Laguette, N., Benichou, S., Basmaciogullari, S. (2009). Human Immunodeficiency Virus Type 1 Nef Incorporation into Virions Does Not Increase Infectivity. J. Virol. 83: 1093-1104 [Abstract] [Full Text]  


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