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Journal of Virology, February 2004, p. 1525-1539, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1525-1539.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Removal of N-Linked Glycosylation Sites in the V1 Region of Simian Immunodeficiency Virus gp120 Results in Redirection of B-Cell Responses to V3

Kelly Stefano Cole,1* Jonathan D. Steckbeck,2 Jennifer L. Rowles,2 Ronald C. Desrosiers,3 and Ronald C. Montelaro2

Departments of Medicine,1 Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261,2 New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 017723

Received 21 May 2003/ Accepted 20 October 2003

One mechanism of immune evasion utilized by human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) envelope glycoproteins is the presence of a dense carbohydrate shield. Accumulating evidence from in vitro and in vivo experiments suggests that alterations in N-linked glycosylation of SIV gp120 can enhance host humoral immune responses that may be involved in immune control. The present study was designed to determine the ability of glycosylation mutant viruses to redirect antibody responses to shielded envelope epitopes. The influence of glycosylation on the maturation and specificity of antibody responses elicited by glycosylation mutant viruses containing mutations of specific N-linked sites in and near the V1 and V2 regions of SIVmac239 gp120 was determined. Results from these studies demonstrated a remarkably similar maturation of antibody responses to native, fully glycosylated envelope proteins. However, analyses of antibodies to defined envelope domains revealed that mutation of glycosylation sites in V1 resulted in increased antibody recognition to epitopes in V1. In addition, we demonstrated for the first time that mutation of glycosylation sites in V1 resulted in a redirection of antibody responses to the V3 loop. Taken together, these results demonstrate that N-linked glycosylation is a determinant of SIV envelope B-cell immunogenicity in addition to in vitro antigenicity. In addition, our results demonstrate that the absence of N-linked carbohydrates at specific sites can influence the exposure of epitopes quite distant in the linear sequence.

* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Diseases, University of Pittsburgh School of Medicine, 3550 Terrace St., S817 Scaife Hall, Pittsburgh, PA 15261. Phone: (412) 383-8583. Fax: (412) 648-8521. E-mail: stefcole{at}pitt.edu.

Journal of Virology, February 2004, p. 1525-1539, Vol. 78, No. 3
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.3.1525-1539.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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