UNSPECIFIED (2005) The C-terminal tail of the gp41 transmembrane envelope glycoprotein of HIV-1 clades A, B, C, and D may exist in two conformations: An analysis of sequence, structure, and function. VIROLOGY, 337 (2). pp. 284-296. ISSN 0042-6822

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Abstract

In addition to the major ectodomain, the gp41 transmembrane glycoprotein of HTV-1 is now known to have a minor ectodomain that is part of the long C-terminal tail. Both ectodomains are highly antigenic, carry neutralizing and non-neutralizing epitopes, and are involved in virus-mediated fusion activity. However, data have so far been biologically based, and derived solely from T cell line-adapted (TCLA), B clade viruses. Here we have carried out sequence and theoretically based structural analyses of 357 gp41 C-terminal sequences of mainly primary isolates of HIV-1 clades A, B, C, and D. Data show that all these viruses have the potential to form a tail loop structure (the minor ectodomain) supported by three, beta-sheet, membrane-spanning domains (MSDs). This means that the first (N-terminal) tyrosine-based sorting signal of the gp41 tail is situated outside the cell membrane and is non-functional, and that gp41 that reaches the cell surface may be recycled back into the cytoplasm through the activity of the second tyrosine-sorting signal. However, we suggest that only a minority of cell-associated gp41 molecules - those destined for incorporation into virions - has 3 MSDs and the minor ectodomain. Most intracellular gp41 has the conventional single MSD, no minor ectodomain, a functional first tyrosine-based sorting signal, and in line with current thinking is degraded intracellularly. The gp41 structural diversity suggested here can be viewed as an evolutionary strategy to minimize HIV-1 envelope glycoprotein expression on the cell surface, and hence possible cytotoxicity and immune attack on the infected cell. (c) 2005 Elsevier Inc. All rights reserved.

Item Type:	Journal Item
Subjects:	Q Science > QR Microbiology > QR355 Virology
Journal or Publication Title:	VIROLOGY
Publisher:	ACADEMIC PRESS INC ELSEVIER SCIENCE
ISSN:	0042-6822
Official Date:	5 July 2005
Dates:	Date Event 5 July 2005 UNSPECIFIED
Volume:	337
Number:	2
Number of Pages:	13
Page Range:	pp. 284-296
Identification Number:	10.1016/j.virol.2005.04.015
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/6882

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