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  Association Between HIV-1 Coreceptor Usage and Resistance to Broadly Neutralizing Antibodies

Pfeifer, N., Walter, H., & Lengauer, T. (2014). Association Between HIV-1 Coreceptor Usage and Resistance to Broadly Neutralizing Antibodies. Journal of Acquired Immune Deficiency Syndromes: JAIDS, 67(2), 107-112. doi:10.1097/QAI.0000000000000283.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0024-5527-A Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0024-552B-2
Genre: Journal Article
Latex : Association Between {HIV}-1 Coreceptor Usage and Resistance to Broadly Neutralizing Antibodies

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 Creators:
Pfeifer, Nico1, Author              
Walter, Hauke2, Author
Lengauer, Thomas1, Author              
Affiliations:
1Computational Biology and Applied Algorithmics, MPI for Informatics, Max Planck Society, ou_40046              
2External Organizations, ou_persistent22              

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 Abstract: Background: Recently discovered broadly neutralizing antibodies have revitalized hopes of developing a universal vaccine against HIV-1. Mainly responsible for new infections are variants only using CCR5 for cell entry, whereas CXCR4-using variants can become dominant in later infection stages. Methods: We performed a statistical analysis on two different previously published data sets. The first data set was a panel of 199 diverse HIV-1 isolates for which IC50 neutralization titers were determined for the broadly neutralizing antibodies VRC01, VRC-PG04, PG9, and PG16. The second data set contained env sequences of viral variants extracted from HIV-1–infected humanized mice treated with the antibody PGT128 and from untreated control mice. Results: For the panel of 199 diverse HIV-1 isolates, we found a statistically significant association between viral resistance to PG9 and PG16 and CXCR4 coreceptor usage (P = 0.0011 and P = 0.0010, respectively). Our analysis of viral variants from HIV-1–infected humanized mice under treatment with the broadly neutralizing antibody PGT128 indicated that certain antibodies might drive a viral population toward developing CXCR4 coreceptor usage capability (P = 0.0011 for the comparison between PGT128 and control measurement). Conclusions: These analyses highlight the importance of accounting for a possible coreceptor usage bias pertaining to the effectiveness of an HIV vaccine and to passive antibody transfer as therapeutic approach.

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Language(s): eng - English
 Dates: 2014-09-242014-10-01
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: DOI: 10.1097/QAI.0000000000000283
PMC: PMC4175123
BibTex Citekey: PfeiferJAIDS2014
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Title: Journal of Acquired Immune Deficiency Syndromes : JAIDS
Source Genre: Journal
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Publ. Info: Philadelphia, PA : Lippincott Williams & Wilkins
Pages: - Volume / Issue: 67 (2) Sequence Number: - Start / End Page: 107 - 112 Identifier: -