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Journal of Virology, November 2009, p. 11588-11598, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.00914-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Truncation of the Membrane-Spanning Domain of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Defines Elements Required for Fusion, Incorporation, and Infectivity{triangledown}

Ling Yue,1,2,3,§ Liang Shang,1,2,3,§ and Eric Hunter1,2,3*

Yerkes National Primate Research Center,1 Department of Pathology and Laboratory Medicine,2 Emory Vaccine Center, Emory University, Atlanta, Georgia 303293

Received 7 May 2009/ Accepted 25 August 2009

The membrane-spanning domain (MSD) of the envelope (Env) glycoprotein from human (HIV) and simian immunodeficiency viruses plays a key role in anchoring the Env complex into the viral membrane but also contributes to its biological function in fusion and virus entry. In HIV type 1 (HIV-1), it has been predicted to span 27 amino acids, from lysine residue 681 to arginine 707, and encompasses an internal arginine at residue 694. By examining a series of C-terminal-truncation mutants of the HIV-1 gp41 glycoprotein that substituted termination codons for amino acids 682 to 708, we show that this entire region is required for efficient viral infection of target cells. Truncation to the arginine at residue 694 resulted in an Env complex that was secreted from the cells. In contrast, a region from residues 681 to 698, which contains highly conserved hydrophobic residues and glycine motifs and extends 4 amino acids beyond 694R, can effectively anchor the protein in the membrane, allow efficient transport to the plasma membrane, and mediate wild-type levels of cell-cell fusion. However, these fusogenic truncated Env mutants are inefficiently incorporated into budding virions. Based on the analysis of these mutants, a "snorkeling" model, in which the flanking charged amino acid residues at 681 and 694 are buried in the lipid while their side chains interact with polar head groups, is proposed for the HIV-1 MSD.

* Corresponding author. Mailing address: Emory Vaccine Center, Emory University, 954 Gatewood Road, Suite 1026, Atlanta, GA 30329. Phone: (404) 727-8587. Fax: (404) 727-9316. E-mail: eric.hunter2{at}emory.edu

{triangledown} Published ahead of print on 2 September 2009.

§ L.Y. and L.S. contributed equally to this work.

Journal of Virology, November 2009, p. 11588-11598, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.00914-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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