scholarly journals N-Linked Glycosylation of the HIV Type-1 gp120 Envelope Glycoprotein as a Major Determinant of CCR5 and CXCR4 Coreceptor Utilization

2001 ◽  
Vol 276 (16) ◽  
pp. 13433-13441 ◽  
Author(s):  
Georgios Pollakis ◽  
Stanley Kang ◽  
Aletta Kliphuis ◽  
Moustapha I. M. Chalaby ◽  
Jaap Goudsmit ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Major Determinant ◽  
Gp120 Envelope ◽  
Cxcr4 Coreceptor ◽  
Hiv Type 1

scholarly journals HIV Type 1 Mother-to-Child Transmission Facilitated by Distinctive Glycosylation Sites in the gp120 Envelope Glycoprotein

2012 ◽  
Vol 28 (7) ◽  
pp. 715-724 ◽  
Author(s):  
Elly Baan ◽  
Anthony de Ronde ◽  
Stanley Luchters ◽  
Joseph Vyankandondera ◽  
Joep M. Lange ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Mother To Child Transmission ◽  
Child Transmission ◽  
Gp120 Envelope ◽  
Glycosylation Sites ◽  
Hiv Type 1 ◽  
Mother To Child

Analysis of the Interaction of Antibodies with a Conserved, Enzymatically Deglycosylated Core of the HIV Type 1 Envelope Glycoprotein 120

1998 ◽  
Vol 14 (3) ◽  
pp. 191-198 ◽  
Author(s):  
JAMES M. BINLEY ◽  
RICHARD WYATT ◽  
ELIZABETH DESJARDINS ◽  
PETER D. KWONG ◽  
WAYNE HENDRICKSON ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Hiv Type 1

scholarly journals Characterization of Human Immunodeficiency Virus Type 1 Monomeric and Trimeric gp120 Glycoproteins Stabilized in the CD4-Bound State: Antigenicity, Biophysics, and Immunogenicity

2007 ◽  
Vol 81 (11) ◽  
pp. 5579-5593 ◽  
Author(s):  
Barna Dey ◽  
Marie Pancera ◽  
Krisha Svehla ◽  
Yuuei Shu ◽  
Shi-Hua Xiang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Binding Site ◽  
Human Immunodeficiency Virus Type ◽  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Bound State ◽  
Wild Type ◽  
Gp120 Envelope ◽  
Immunodeficiency Virus

ABSTRACT The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations in several gp120 envelope glycoprotein contexts. The gp120 glycoproteins with the T257S-plus-S375W double mutation (T257S+S375W) have a superior antigenic profile compared to the originally identified single S375W replacement in terms of enhanced recognition by the broadly neutralizing CD4 binding-site antibody b12. Isothermal titration calorimetry measuring the entropy of the gp120 interaction with CD4 indicated that the double mutant was also stabilized into the CD4-bound state, with increasing relative fixation between core, full-length monomeric, and full-length trimeric versions of gp120. A significant increase in gp120 affinity for CD4 was also observed for the cavity-filling mutants relative to wild-type gp120. The most conformationally constrained T257S+S375W trimeric gp120 proteins were selected for immunogenicity analysis in rabbits and displayed a trend of improvement relative to their wild-type counterparts in terms of eliciting neutralizing antibodies. Together, the results suggest that conformational stabilization may improve the ability of gp120 to elicit neutralizing antibodies.

Effects of HIV Type 1 Envelope Glycoprotein Proteolytic Processing on Antigenicity

2003 ◽  
Vol 19 (3) ◽  
pp. 217-226 ◽  
Author(s):  
Zhihai Si ◽  
Ngoc Phan ◽  
Enko Kiprilov ◽  
Joseph Sodroski
Keyword(s):  
Envelope Glycoprotein ◽  
Proteolytic Processing ◽  
Hiv Type 1

scholarly journals Reevaluation of Amino Acid Variability of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein and Prediction of New Discontinuous Epitopes

2000 ◽  
Vol 74 (9) ◽  
pp. 4335-4350 ◽  
Author(s):  
Yumi Yamaguchi-Kabata ◽  
Takashi Gojobori
Keyword(s):  
Human Immunodeficiency Virus ◽  
Amino Acid ◽  
Envelope Glycoprotein ◽  
Nonsynonymous Substitutions ◽  
Gp120 Envelope ◽  
Immunodeficiency Virus ◽  
Α Helix ◽  
Synonymous And Nonsynonymous Substitutions ◽  
Discontinuous Epitopes

ABSTRACT To elucidate the evolutionary mechanisms of the human immunodeficiency virus type 1 gp120 envelope glycoprotein at the single-site level, the degree of amino acid variation and the numbers of synonymous and nonsynonymous substitutions were examined in 186 nucleotide sequences for gp120 (subtype B). Analyses of amino acid variabilities showed that the level of variability was very different from site to site in both conserved (C1 to C5) and variable (V1 to V5) regions previously assigned. To examine the relative importance of positive and negative selection for each amino acid position, the numbers of synonymous and nonsynonymous substitutions that occurred at each codon position were estimated by taking phylogenetic relationships into account. Among the 414 codon positions examined, we identified 33 positions where nonsynonymous substitutions were significantly predominant. These positions where positive selection may be operating, which we call putative positive selection (PS) sites, were found not only in the variable loops but also in the conserved regions (C1 to C4). In particular, we found seven PS sites at the surface positions of the α-helix (positions 335 to 347 in the C3 region) in the opposite face for CD4 binding. Furthermore, two PS sites in the C2 region and four PS sites in the C4 region were detected in the same face of the protein. The PS sites found in the C2, C3, and C4 regions were separated in the amino acid sequence but close together in the three-dimensional structure. This observation suggests the existence of discontinuous epitopes in the protein's surface including this α-helix, although the antigenicity of this area has not been reported yet.

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