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Journal of Virology, March 2005, p. 3627-3638, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3627-3638.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Functional Domains within the Human Immunodeficiency Virus Type 2 Envelope Protein Required To Enhance Virus Production

Paolo Abada,1 Beth Noble,1,2 and Paula M. Cannon1,2,3*

Department of Biochemistry and Molecular Biology,1 Department of Pediatrics, University of Southern California Keck School of Medicine,3 Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, California2

Received 21 July 2004/ Accepted 3 November 2004

Primate lentiviruses code for a protein that stimulates virus production. In human immunodeficiency virus type 1 (HIV-1), the activity is provided by the accessory protein, Vpu, while in HIV-2 and simian immunodeficiency virus it is a property of the envelope (Env) glycoprotein. Using a group of diverse retroviruses and cell types, we have confirmed the functional equivalence of the two proteins. However, despite these similarities, the two proteins have markedly different functional domains. While the Vpu activity is associated primarily with its membrane-spanning region, we have determined that the HIV-2 Env activity requires both the cytoplasmic tail and ectodomain of the protein, with the membrane-spanning domain being less important. Within the Env cytoplasmic tail, we further defined the necessary sequence as a membrane-proximal tyrosine-based motif. Providing the two Env regions separately as distinct CD8 chimeric proteins did not increase virus release. This suggests that the two domains must be either contained within a single protein or closely associated within a multiprotein oligomer, such as the Env trimer, in order to function. Finally, we observed that wild-type levels of incorporation of the HIV-2 Env into budding viruses were not required for this activity.

* Corresponding author. Mailing address: Department of Research Immunology and Bone Marrow Transplantation, Childrens Hospital Los Angeles, 4650 Sunset Blvd., Mailstop 62, Los Angeles, CA 90027. Phone: (323) 669-5916. Fax: (323) 660-8736. E-mail: pcannon{at}chla.usc.edu.

Journal of Virology, March 2005, p. 3627-3638, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3627-3638.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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  • Richards, K. H., Clapham, P. R. (2007). Effects of vpu start-codon mutations on human immunodeficiency virus type 1 replication in macrophages. J. Gen. Virol. 88: 2780-2792 [Abstract] [Full Text]  
  • Noble, B., Abada, P., Nunez-Iglesias, J., Cannon, P. M. (2006). Recruitment of the Adaptor Protein 2 Complex by the Human Immunodeficiency Virus Type 2 Envelope Protein Is Necessary for High Levels of Virus Release. J. Virol. 80: 2924-2932 [Abstract] [Full Text]  


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