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Journal of Virology, February 2005, p. 1686-1700, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1686-1700.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

CCR5, GPR15, and CXCR6 Are Major Coreceptors of Human Immunodeficiency Virus Type 2 Variants Isolated from Individuals with and without Plasma Viremia

H. Blaak,1* P. H. M. Boers,1 R. A. Gruters,1 H. Schuitemaker,2 M. E. van der Ende,3 and A. D. M. E. Osterhaus1

Department of Virology,1 Department of Internal Medicine, Erasmus MC, Rotterdam,3 Sanquin Research at CLB and the Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands2

Received 23 January 2004/ Accepted 10 September 2004

Human immunodeficiency virus type 2 (HIV-2) is generally considered capable of using a broad range of coreceptors. Since HIV-2 variants from individuals with nonprogressive infection were not studied previously, the possibility that broad coreceptor usage is a property of variants associated with progressive infection could not be excluded. To test this, we determined the coreceptor usage of 43 HIV-2 variants isolated from six long-term-infected individuals with undetectable plasma viremia. Using GHOST indicator cells, we showed for the first time that the only coreceptors efficiently used by low-pathogenic HIV-2 variants are CCR5, GPR15 (BOB), and CXCR6 (BONZO). Surprisingly, control HIV-2 variants (n = 45) isolated from seven viremic individuals also mainly used these three coreceptors, whereas use of CCR1, CCR2b, or CCR3 was rare. Nearly a quarter of all HIV-2 variants tested could infect the parental GHOST cells, which could be partially explained by CXCR4 usage. Use of CXCR4 was observed only for HIV-2 variants from viremic individuals. Thirty-eight variants from aviremic and viremic HIV-2-infected individuals were additionally tested in U87 cells. All except one were capable of infecting the parental U87 cells, often with high efficiency. When virus production in parental cells was regarded as background in the coreceptor-transduced cell lines, the results in U87 cells were largely in agreement with the findings in GHOST cells. HIV-2 isolates from aviremic individuals commonly use as coreceptors CCR5, GPR15, and CXCR6, as well as an unidentified receptor expressed by U87 cells. Broad coreceptor usage, therefore, does not appear to be associated with pathogenicity of HIV-2.

* Corresponding author. Mailing address: Department of Virology, Room Ee1742a, Erasmus MC, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. Phone: 31-10-4088068. Fax: 31-10-4089485. E-mail: h.blaak{at}erasmusmc.nl.

Journal of Virology, February 2005, p. 1686-1700, Vol. 79, No. 3
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.3.1686-1700.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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