16th International AIDS Conference Toronto, Canada - August 13 - 18, 2006

CXCR4 ANTAGONIST-INDUCED CORECEPTOR SWITCH FROM X4 TO R5 PHENOTYPE IN VITRO DETERMINED BY A SINGLE AMINO ACID SUBSTITUTION IN THE V3 REGION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 gp120

Int Conf AIDS. 2006 Aug 13-18;16 Abstract No. MoAa0104

Maeda Y., Yusa K., Harada S.
Kumamoto University, Graduate School of Medical Sciences, Department of Medical Virology, Kumamoto, Japan

BACKGROUND: The disease progression of HIV-1 infection is largely associated with a switch of coreceptor usage by HIV-1 from CCR5 to CXCR4. However, the coreceptor switch has not been well reproduced in vitro under the selection pressure of CCR5 or CXCR4 antagonists.

METHODS: For the selection of coreceptor switch mutants, an R5X4 variant (89.6 strain) was passaged in the presence of a CXCR4 antagonist T140 using PM1/CCR5 cell line which is highly susceptible to R5 variants.

RESULTS: An isolated mutant harbored a single amino acid substitution in the V3 region of the Env (Arginine 308 to Serine, R308S). Luciferase-reporter HIV-1 pseudotyped with the mutant Env showed that the substitution totally conferred resistance to CXCR4 antagonists but increased sensitivity to a CCR5 antagonist TAK-779 in the infection of the cells expressing both CCR5 and CXCR4. Analyses using the cells expressing a single coreceptor showed that the virus with the mutation predominantly utilized CCR5 with retaining CXCR4 usage, and had higher affinity for CCR5 than CXCR4.

CONCLUSIONS: These results indicated that the coreceptor switch from X4 to R5 phenotype was easily occurred in vitro when intermediate phenotypes of HIV-1 (R5X4 variants) were used.

Download PDF of this abstract.

2006-08-13
MoAa0104

Copyright © 2006 - International AIDS Society (IAS). All information and content relating to the abstracts from the 16th International AIDS Conference, such as text, graphics, logos, button icons, images, audio clips, and software is protected by copyright. Permission is hereby granted for the non-commercial use or reproduction of the information on this web site, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.

AEGiS is a 501c(3) not-for-profit organization made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, GlaxoSmithKline, the National Library of Medicine, Roche / Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 2006. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 2006. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. Permission is hereby granted for the non-commercial use or reproduction of the information herein, provided that the use of such information is accompanied by an acknowledgement that IAS is the source of the information and the name of the author of the article.