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Cited by 303

The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.

HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use

Open access
Trkola, Alexandra, Kuhmann, Shawn E., Strizki, Julie M., Maxwell, Elizabeth, Ketas, Tom, Morgan, Tom, Pugach, Pavel, Xu, Serena, Wojcik, Lisa, Tagat, Jayaram, Palani, Anandan, Shapiro, Sherry, Clader, John W., McCombie, Stuart, Reyes, Gregory R., Baroudy, Bahige M., Moore, John P.·2002·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.012519099
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Abstract

To study HIV-1 escape from a coreceptor antagonist, the R5 primary isolate CC1/85 was passaged in peripheral blood mononuclear cells with increasing concentrations of the CCR5-specific small molecule inhibitor, AD101. By 19 passages, an escape mutant emerged with a >20,000-fold resistance to AD101. This virus was cross-resistant to a related inhibitor, SCH-C, and partially resistant to RANTES but still sensitive to CCR5-specific mAbs. The resistant phenotype was stable; the mutant virus retained AD101 resistance during nine additional passages of culture in the absence of inhibitor. Replication of the escape mutant in peripheral blood mononuclear cells completely depended on CCR5 expression and did not occur in cells from CCR5-Δ32 homozygous individuals. The escape mutant was unable to use CXCR4 or any other tested coreceptor to enter transfected cells. Acquisition of CXCR4 use is not the dominant in vitro escape pathway for a small molecule CCR5 entry inhibitor. Instead, HIV-1 acquires the ability to use CCR5 despite the inhibitor, first by requiring lower levels of CCR5 for entry and then probably by using the drug-bound form of the receptor.

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Crossref · 10.1073/pnas.012519099

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Metadata

Authors
Trkola, A., Kuhmann, S. E., Strizki, J. M., Maxwell, E., Ketas, T., Morgan, T., Pugach, P., Xu, S., Wojcik, L., Tagat, J., Palani, A., Shapiro, S., Clader, J. W., McCombie, S., Reyes, G. R., Baroudy, B. M., & Moore, J. P.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2002-01-08
Volume
99
Issue
1
Pages
395-400
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.012519099
OpenAlex
W1966515400
Cited by
303
References
33
FWCI
10.14
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. https://app.cochat.ai/papers/10.1073/pnas.012519099
The paper
Trkola, A., Kuhmann, S. E., Strizki, J. M., Maxwell, E., Ketas, T., Morgan, T., Pugach, P., Xu, S., Wojcik, L., Tagat, J., Palani, A., Shapiro, S., Clader, J. W., McCombie, S., Reyes, G. R., Baroudy, B. M., & Moore, J. P. (2002). HIV-1 escape from a small molecule, CCR5-specific entry inhibitor does not involve CXCR4 use. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.012519099

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.