JVI Figure table search 04
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hoffman, N. G.
Right arrow Articles by Swanstrom, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hoffman, N. G.
Right arrow Articles by Swanstrom, R.
Journal of Virology, April 2002, p. 3852-3864, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3852-3864.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Variability in the Human Immunodeficiency Virus Type 1 gp120 Env Protein Linked to Phenotype-Associated Changes in the V3 Loop

Noah G. Hoffman,1,2 Francoise Seillier-Moiseiwitsch,2,3,{dagger} JaeHyung Ahn,3 Jason M. Walker,2 and Ronald Swanstrom1,2*

Department of Microbiology and Immunology,1 UNC Center for AIDS Research,2 Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-72953

Received 13 July 2001/ Accepted 21 December 2001

Isolates of human immunodeficiency virus type 1 (HIV-1) are classified according to the chemokine receptor (coreceptor) used in conjunction with CD4 to target and enter cells: viruses using CCR5 and CXCR4 are classified as R5 and X4, respectively. The major determinant of entry-related HIV-1 phenotypes is known to reside in the third variable region of gp120 (V3). It is clear, however, that positions outside of V3 play some role in influencing phenotype, although marked context dependence and extensive variability among HIV-1 isolates have made the identification of these positions difficult. We used the presence of previously described substitutions in V3 to classify a large set of HIV-1 subtype B gp120 sequences available in public databases as X4-like or R5-like. Using these classifications, we searched for positions outside of V3 where either amino acid composition or variability differed significantly among sequences of different inferred phenotypes. Our approach took the epidemiological relationships among sequences into account. A cluster of positions linked to changes in V3 was identified between amino acids 190 and 204 of gp120, immediately C-terminal of V2; changes at position 440 in C4 were also linked to inferred phenotype. Structural data place these positions at the coreceptor-binding face of gp120 in a surface-exposed location. We also noted a significant increase in net positive charge in a highly variable region of V2. This study both confirms previous observations and predicts specific positions that contribute to a functional relationship between V3, V2, and C4.

* Corresponding author. Mailing address: 22-006 LCCC CB# 7295, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295. Phone: (919) 966-5710. Fax: (919) 966-8212. E-mail: risunc{at}med.unc.edu.

{dagger} Present address: Department of Mathematics and Statistics, University of Maryland, Baltimore County, Baltimore, Md.

Journal of Virology, April 2002, p. 3852-3864, Vol. 76, No. 8
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.8.3852-3864.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. Mol. Cell. Biol. Microbiol. Mol. Biol. Rev.
Clin. Vaccine Immunol. ALL ASM JOURNALS

Copyright © 2002 by the American Society for Microbiology. All rights reserved.