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Journal of Virology, January 2007, p. 525-531, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01983-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Increased Neutralization Sensitivity of Recently Emerged CXCR4-Using Human Immunodeficiency Virus Type 1 Strains Compared to Coexisting CCR5-Using Variants from the Same Patient{triangledown}

Evelien M. Bunnik, Esther D. Quakkelaar, Ad C. van Nuenen, Brigitte Boeser-Nunnink, and Hanneke Schuitemaker*

Department of Clinical Viro-Immunology, Sanquin Research and Landsteiner Laboratory at the Academic Medical Center, University of Amsterdam and Center for Infection and Immunity Amsterdam (CINIMA), Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands

Received 12 September 2006/ Accepted 24 October 2006

CXCR4-using (X4) human immunodeficiency virus type 1 (HIV-1) variants evolve from CCR5-using (R5) variants relatively late in the natural course of infection in 50% of HIV-1 subtype B-infected individuals and subsequently coexist with R5 HIV-1 variants. This relatively late appearance of X4 HIV-1 variants is poorly understood. Here we tested the neutralization sensitivity for soluble CD4 (sCD4) and the broadly neutralizing antibodies IgG1b12, 2F5, 4E10, and 2G12 of multiple coexisting clonal R5 and (R5)X4 (combined term for monotropic X4 and dualtropic R5X4 viruses) HIV-1 variants that were obtained at two time points after the first appearance of X4 variants in five participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS. Recently emerged (R5)X4 viruses were significantly more sensitive to neutralization by the CD4-binding-site-directed agents sCD4 and IgG1b12 than their coexisting R5 viruses. This difference was less pronounced at the later time point. Early (R5)X4 variants from two out of four patients were also highly sensitive to neutralization by autologous serum (50% inhibition at serum dilutions of >200). Late (R5)X4 viruses from these two patients were neutralized at lower serum dilutions, which suggested escape of X4 variants from humoral immunity. Autologous neutralization of coexisting R5 and (R5)X4 variants was not observed in the other patients. In conclusion, the increased neutralization sensitivity of HIV-1 variants during the transition from CCR5 usage to CXCR4 usage may imply an inhibitory role for humoral immunity in HIV-1 phenotype evolution in some patients, thus potentially contributing to the late emergence of X4 variants.

* Corresponding author. Mailing address: Dept. Clinical Viro-Immunology, Sanquin Research, Plesmanlaan 125, 1066 CX Amsterdam, The Netherlands. Phone: 31-20-5123317. Fax: 31-20-5123310. E-mail: h.schuitemaker{at}sanquin.nl.

{triangledown} Published ahead of print on 1 November 2006.

Journal of Virology, January 2007, p. 525-531, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.01983-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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