V3-Independent competitive resistance of a Dual-X4 HIV-1 to the CXCR4 inhibitor AMD3100

2Citations
Citations of this article
5Readers
Mendeley users who have this article in their library.

Abstract

A CXCR4 inhibitor-resistant HIV-1 was isolated from a dual-X4 HIV-1 in vitro. The resistant variant displayed competitive resistance to the CXCR4 inhibitor AMD3100, indicating that the resistant variant had a higher affinity for CXCR4 than that of the wild-type HIV-1. Amino acid sequence analyses revealed that the resistant variant harbored amino acid substitutions in the V2, C2, and C4 regions, but no remarkable changes in the V3 loop. Site-directed mutagenesis confirmed that the changes in the C2 and C4 regions were principally involved in the reduced sensitivity to AMD3100. Furthermore, the change in the C4 region was associated with increased sensitivity to soluble CD4, and profoundly enhanced the entry efficiency of the virus. Therefore, it is likely that the resistant variant acquired the higher affinity for CD4/CXCR4 by the changes in non-V3 regions. Taken together, a CXCR4 inhibitor-resistant HIV-1 can evolve using a non-V3 pathway. © 2014 Maeda et al.

Cite

CITATION STYLE

APA

Maeda, Y., Terasawa, H., Nakano, Y., Monde, K., Yusa, K., Oka, S., … Harada, S. (2014). V3-Independent competitive resistance of a Dual-X4 HIV-1 to the CXCR4 inhibitor AMD3100. PLoS ONE, 9(2). https://doi.org/10.1371/journal.pone.0089515

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free