HIV-1 envelope glycoprotein signatures that correlate with the development of cross-reactive neutralizing activity

Current HIV-1 envelope glycoprotein (Env) vaccines are unable to induce cross-reactive neutralizing antibodies. However, such antibodies are elicited in 10-30% of HIV-1 infected individuals, but it is unknown why these antibodies are induced in some individuals and not in others. We hypothesized tha...

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Bibliographic Details
Published in:Retrovirology 2013-09, Vol.10 (1), p.102-102, Article 102
Main Authors: van den Kerkhof, Tom L G M, Feenstra, K Anton, Euler, Zelda, van Gils, Marit J, Rijsdijk, Linda W E, Boeser-Nunnink, Brigitte D, Heringa, Jaap, Schuitemaker, Hanneke, Sanders, Rogier W
Format: Article
Language:English
Subjects:
Acquired immune deficiency syndrome
AIDS
AIDS vaccines
Amino acid sequence
Analysis
Antibodies
Antibodies, Neutralizing - immunology
Antigenic determinants
Binding sites
Bioinformatics
Cohort Studies
Cross Reactions
Drug therapy
env Gene Products, Human Immunodeficiency Virus - genetics
env Gene Products, Human Immunodeficiency Virus - immunology
Glycoproteins
Glycoproteins - genetics
Glycoproteins - immunology
HIV
HIV Antibodies - immunology
HIV infection
HIV-1 - genetics
HIV-1 - immunology
Human immunodeficiency virus
Human immunodeficiency virus 1
Humans
Infections
Molecular weight
Physiological aspects
Protein folding
Risk factors
Viral antibodies
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Summary:Current HIV-1 envelope glycoprotein (Env) vaccines are unable to induce cross-reactive neutralizing antibodies. However, such antibodies are elicited in 10-30% of HIV-1 infected individuals, but it is unknown why these antibodies are induced in some individuals and not in others. We hypothesized that the Envs of early HIV-1 variants in individuals who develop cross-reactive neutralizing activity (CrNA) might have unique characteristics that support the induction of CrNA. We retrospectively generated and analyzed env sequences of early HIV-1 clonal variants from 31 individuals with diverse levels of CrNA 2-4 years post-seroconversion. These sequences revealed a number of Env signatures that coincided with CrNA development. These included a statistically shorter variable region 1 and a lower probability of glycosylation as implied by a high ratio of NXS versus NXT glycosylation motifs. Furthermore, lower probability of glycosylation at position 332, which is involved in the epitopes of many broadly reactive neutralizing antibodies, was associated with the induction of CrNA. Finally, Sequence Harmony identified a number of amino acid changes associated with the development of CrNA. These residues mapped to various Env subdomains, but in particular to the first and fourth variable region as well as the underlying α2 helix of the third constant region. These findings imply that the development of CrNA might depend on specific characteristics of early Env. Env signatures that correlate with the induction of CrNA might be relevant for the design of effective HIV-1 vaccines.
ISSN:1742-4690
1742-4690
DOI:10.1186/1742-4690-10-102