The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
Development and Characterization of a Novel Single-Cycle Recombinant-Virus Assay To Determine Human Immunodeficiency Virus Type 1 Coreceptor Tropism
Open accessAbstract
Most human immunodeficiency virus type 1 (HIV-1) strains require either the CXCR4 or CCR5 chemokine receptor to efficiently enter cells. Blocking viral binding to these coreceptors is an attractive therapeutic target. Currently, several coreceptor antagonists are being evaluated in clinical trials that require characterization of coreceptor tropism for enrollment. In this report, we describe the development of an automated and accurate procedure for determining HIV-1 coreceptor tropism (Trofile) and its validation for routine laboratory testing. HIV-1 pseudoviruses are generated using full-length env genes derived from patient virus populations. Coreceptor tropism is determined by measuring the abilities of these pseudovirus populations to efficiently infect CD4 + /U87 cells expressing either the CXCR4 or CCR5 coreceptor. Viruses exclusively and efficiently infecting CXCR4 + /CD4 + /U87 cells are designated X4-tropic. Conversely, viruses exclusively and efficiently infecting CCR5 + /CD4 + /U87 cells are designated R5-tropic. Viruses capable of infecting both CXCR4 + /CD4 + /U87 and CCR5 + /CD4 + /U87 cells are designated dual/mixed-tropic. Assay accuracy and reproducibility were established by evaluating the tropisms of well-characterized viruses and the variability among replicate results from samples tested repeatedly. The viral subtype, hepatitis B virus or hepatitis C virus coinfection, and the plasma viral load did not affect assay performance. Minority subpopulations with alternate tropisms were reliably detected when present at 5 to 10%. The plasma viral load above which samples can be amplified efficiently in the Trofile assay is 1,000 copies per ml of plasma. Trofile has been automated for high-throughput use; it can be used to identify patients most likely to benefit from treatment regimens that include a coreceptor inhibitor and to monitor patients on treatment for the emergence of resistant virus populations that switch coreceptor tropism.
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Cites
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Cited by
Hirsch, M. S., Günthard, H. F., Schapiro, J. M., Brun‐Vézinet, F., Clotet, B., Hammer, S. M., Johnson, V. A., Kuritzkes, D. R., Mellors, J. W., Pillay, D., et al. (2008) · Clinical Infectious Diseases · doi:10.1086/589297 · Cited by 573
Subgroup Analyses of Maraviroc in Previously Treated R5 HIV-1 Infection
Fätkenheuer, G., Nelson, M., Lazzarin, A., Konourina, I., Hoepelman, A. I. M., Lampiris, H., Hirschel, B., Tebas, P., Raffi, F., Trottier, B., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0803154 · Cited by 364
HIV-1 Antiretroviral Resistance: Scientific Principles and Clinical Applications
Tang, M. W., & Shafer, R. W. (2012) · Drugs · doi:10.2165/11633630-000000000-00000 · Cited by 326
Barrett, J. R., Belij-Rammerstorfer, S., Dold, C., Ewer, K. J., Folegatti, P. M., Gilbride, C., Halkerston, R., Hill, J., Jenkin, D., Stockdale, L., et al. (2021) · Nature Medicine · doi:10.1038/s41591-020-01179-4 · Cited by 315
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Metadata
- Authors
- Whitcomb, J. M., Huang, W., Fransen, S., Limoli, K., Toma, J., Wrin, T., Chappey, C., Kiss, L. D. B., Paxinos, E. E., & Petropoulos, C. J.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2007-02
- Volume
- 51
- Issue
- 2
- Pages
- 566-575
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- OpenAlex
- W2169054534
- Cited by
- 356
- References
- 45
- FWCI
- 11.24
- Type
- journal article
- Language
- en
- Open access
- green
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- Whitcomb, J. M., Huang, W., Fransen, S., Limoli, K., Toma, J., Wrin, T., Chappey, C., Kiss, L. D. B., Paxinos, E. E., & Petropoulos, C. J. (2007). Development and Characterization of a Novel Single-Cycle Recombinant-Virus Assay To Determine Human Immunodeficiency Virus Type 1 Coreceptor Tropism. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/aac.00853-06
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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