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Positive in vivo selection of the HIV-1 envelope protein gp120 occurs at surface-exposed regions


Joos, B; Fischer, M; Schweizer, A; Kuster, H; Boni, J; Wong, J K; Weber, R; Trkola, A; Gunthard, H F (2007). Positive in vivo selection of the HIV-1 envelope protein gp120 occurs at surface-exposed regions. Journal of Infectious Diseases, 196(2):313-320.

Abstract

The rapid evolution of human immunodeficiency virus (HIV) envelope represents a major challenge to vaccine and drug development, particularly because the underlying mechanisms are not completely understood. To explore whether distinct patterns of positive selection within the envelope glycoprotein (gp) 120 exist and are associated with functionally relevant domains, we conducted a long-term survey of sequence evolution in 20 HIV-1-infected persons who interrupted antiretroviral therapy. In total, 1753 clonal sequences encompassing the C2-V3-C3 region of gp120 were derived. Strikingly, positively selected amino acids mapped almost exclusively (P=.0003) to externally accessible residues on the gp120 crystal structure. The current understanding of envelope structure and function associates the main determinants of viral entry and the targets for neutralizing antibodies with these exterior regions of gp120, strongly suggesting that the observed adaptive evolution of these sites occurs in response to respective selective forces.

The rapid evolution of human immunodeficiency virus (HIV) envelope represents a major challenge to vaccine and drug development, particularly because the underlying mechanisms are not completely understood. To explore whether distinct patterns of positive selection within the envelope glycoprotein (gp) 120 exist and are associated with functionally relevant domains, we conducted a long-term survey of sequence evolution in 20 HIV-1-infected persons who interrupted antiretroviral therapy. In total, 1753 clonal sequences encompassing the C2-V3-C3 region of gp120 were derived. Strikingly, positively selected amino acids mapped almost exclusively (P=.0003) to externally accessible residues on the gp120 crystal structure. The current understanding of envelope structure and function associates the main determinants of viral entry and the targets for neutralizing antibodies with these exterior regions of gp120, strongly suggesting that the observed adaptive evolution of these sites occurs in response to respective selective forces.

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Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > Institute of Medical Virology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:15 July 2007
Deposited On:11 Feb 2008 12:28
Last Modified:05 Apr 2016 12:22
Publisher:University of Chicago Press
ISSN:0022-1899
Additional Information:© 2007 by the Infectious Diseases Society of America
Publisher DOI:10.1086/518935
PubMed ID:17570120
Permanent URL: http://doi.org/10.5167/uzh-2180

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