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Updated: May 14, 2026
Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3
Published on: December 27, 2010
Characterization of a dual-tropic human immunodeficiency virus (HIV-1) strain derived from the prototypical X4
Shi-hua Xiang1, Beatriz Pacheco, Dane Bowder
1Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Department of Microbiology and Immunobiology, Division of AIDS, Harvard Medical School, Boston, MA 02215, USA. sxiang2@unl.edu
Abstract:
Human immunodeficiency virus type 1 (HIV-1) coreceptor usage and tropism can be modulated by the V3 loop sequence of the gp120 exterior envelope glycoprotein. For coreceptors, R5 viruses use CCR5, X4 viruses use CXCR4, and dual-tropic (R5X4) viruses use either CCR5 or CXCR4. To understand the requirements for dual tropism, we derived and analyzed a dual-tropic variant of an X4 virus. Changes in the V3 base, which allow gp120 to interact with the tyrosine-sulfated CCR5 N-terminus, and deletion of residues 310/311 in the V3 tip were necessary for efficient CCR5 binding and utilization. Thus, both sets of V3 changes allowed CCR5 utilization with retention of the ability to use CXCR4. We also found that the stable association of gp120 with the trimeric envelope glycoprotein complex in R5X4 viruses, as in X4 viruses, is less sensitive to V3 loop changes than gp120-trimer association in R5 viruses.
