This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Laguette, N.
Right arrow Articles by Basmaciogullari, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laguette, N.
Right arrow Articles by Basmaciogullari, S.

 Previous Article  |  Next Article 

Journal of Virology, January 2009, p. 1093-1104, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01633-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Nef Incorporation into Virions Does Not Increase Infectivity {triangledown}

Nadine Laguette,1,2 Serge Benichou,1,2* and Stéphane Basmaciogullari1,2*

Institut Cochin, CNRS UMR8104, Université Paris Descartes, Paris, France,1 INSERM U567, Paris, France2

Received 31 July 2008/ Accepted 26 October 2008

The viral protein Nef contributes to the optimal infectivity of human and simian immunodeficiency viruses. The requirement for Nef during viral biogenesis particles suggests that Nef might play a role in this process. Alternatively, because Nef is incorporated into viruses, it might play a role when progeny virions reach target cells. We challenged these hypotheses by manipulating the amounts of Nef incorporated in viruses while keeping its expression level constant in producer cells. This was achieved by forcing the incorporation of Nef into viral particles by fusing a Vpr sequence to the C-terminal end of Nef. A cleavage site for the viral protease was introduced between Nef and Vpr to allow the release of Nef fragments from the fusion protein during virus maturation. We show that the resulting Nef-CS-Vpr fusion partially retains the ability of Nef to downregulate cell surface CD4 and that high amounts of Nef-CS-Vpr are incorporated into viral particles compared with what is seen for wild-type Nef. The fusion protein is processed during virion maturation and releases Nef fragments similar to those found in viruses produced in the presence of wild-type Nef. Unlike viruses produced in the presence of wild-type Nef, viruses produced in the presence of Nef-CS-Vpr do not have an increase in infectivity and are as poorly infectious as viruses produced in the absence of Nef. These findings demonstrate that the presence of Nef in viral particles is not sufficient to increase human immunodeficiency virus type 1 infectivity and suggest that Nef plays a role during the biogenesis of viral particles.

* Corresponding author. Mailing address: Institut Cochin, 27 Rue du Faubourg Saint-Jacques, 75014 Paris, France. Phone: (33) 1 40 51 65 80. Fax: (33) 1 40 51 65 70. E-mail for Stéphane Basmaciogullari: stephane.basmaciogullari{at}inserm.fr. E-mail for Serge Benichou: serge.benichou{at}inserm.fr

{triangledown} Published ahead of print on 5 November 2008.

Journal of Virology, January 2009, p. 1093-1104, Vol. 83, No. 2
0022-538X/09/$08.00+0     doi:10.1128/JVI.01633-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»