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Journal of Virology, March 2006, p. 2924-2932, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2924-2932.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Recruitment of the Adaptor Protein 2 Complex by the Human Immunodeficiency Virus Type 2 Envelope Protein Is Necessary for High Levels of Virus Release{dagger}

Beth Noble,1,3 Paolo Abada,1 Juan Nunez-Iglesias,1,3 and Paula M. Cannon1,2,3*

Department of Biochemistry and Molecular Biology,1 Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California,2 Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, California3

Received 13 October 2005/ Accepted 15 December 2005

The envelope (Env) protein of human immunodeficiency virus type 2 (HIV-2) and the HIV-1 Vpu protein stimulate the release of retroviral particles from human cells that restrict virus production, an activity that we call the enhancement of virus release (EVR). We have previously shown that two separate domains in the HIV-2 envelope protein are required for this activity: a glycine-tyrosine-x-x-hydrophobic (GYxx{theta}) motif in the cytoplasmic tail and an unmapped region in the ectodomain of the protein. We here report that the cellular partner of the GYxx{theta} motif is the adaptor protein complex AP-2. The mutation of this motif or the depletion of AP-2 by RNA interference abrogated EVR activity and changed the cellular distribution of the Env from a predominantly punctate pattern to a more diffuse distribution. Since the L domain of equine infectious anemia virus (EIAV) contains a Yxx{theta} motif that interacts with AP-2, we used both wild-type and L domain-defective particles of HIV-1 and EIAV to examine whether the HIV-2 Env EVR function was analogous to L domain activity. We observed that the production of all particles was stimulated by HIV-2 Env or Vpu, suggesting that the L domain and EVR activities play independent roles in the release of retroviruses. Interestingly, we found that the cytoplasmic tail of the murine leukemia virus (MLV) Env could functionally substitute for the HIV-2 Env tail, but it did so in a manner that did not require a Yxx{theta} motif or AP-2. The cellular distribution of the chimeric HIV-2/MLV Env was significantly less punctate than the wild-type Env, although confocal analysis revealed an overlap in the steady-state locations of the two proteins. Taken together, these data suggest that the essential GYxx{theta} motif in the HIV-2 Env tail recruits AP-2 in order to direct Env to a cellular pathway or location that is necessary for its ability to enhance virus release but that an alternate mechanism provided by the MLV Env tail can functionally substitute.

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

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, March 2006, p. 2924-2932, Vol. 80, No. 6
0022-538X/06/$08.00+0     doi:10.1128/JVI.80.6.2924-2932.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Le Tortorec, A., Neil, S. J. D. (2009). Antagonism to and Intracellular Sequestration of Human Tetherin by the Human Immunodeficiency Virus Type 2 Envelope Glycoprotein. J. Virol. 83: 11966-11978 [Abstract] [Full Text]  
  • 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]  


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