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Journal of Virology, May 2009, p. 5028-5034, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02551-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Role of Natural Killer Cells in a Cohort of Elite Suppressors: Low Frequency of the Protective KIR3DS1 Allele and Limited Inhibition of Human Immunodeficiency Virus Type 1 Replication In Vitro {triangledown}

Karen A. O'Connell,1 Yefei Han,1 Thomas M. Williams,2 Robert F. Siliciano,1,3 and Joel N. Blankson1*

Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,1 Department of Pathology, University of New Mexico School of Medicine, and Tricore Reference Laboratories, Albuquerque, New Mexico 87131,2 Howard Hughes Medical Institute, Baltimore, Maryland 212053

Received 11 December 2008/ Accepted 3 February 2009

Natural killer (NK) cells are associated with the innate immune response and are important in many viral infections. Recent studies indicate that NK cells can control human immunodeficiency virus type 1 (HIV-1) replication. We studied the effect of NK cells on HIV-1 replication in a subpopulation of HIV-1-infected individuals termed elite suppressors (ES) or elite controllers. These patients maintain a clinically undetectable viral load without treatment and thus provide a fascinating cohort in which to study the immunological response to HIV-1. Using an autologous system, we analyzed the effects of NK cells and CD8+ T cells on viral replication in CD4+ T lymphoblasts. Although we had postulated that NK cells of ES would be highly effective at controlling viral replication, we found that NK cells from some, but not all, ES were capable of inhibiting replication in the presence of interleukin-2, and the inhibition was less robust than that mediated by CD8+ T cells. Additionally, we examined whether particular alleles of the KIR receptors, specifically KIR3DS1 and KIR3DL1, or allele-ligand combinations correlated with the control of HIV-1 replication by NK cells and whether any specific KIR alleles were overrepresented in ES. Our ES cohort did not differ from the general population with respect to the frequency of individual KIR. However, of the eight ES studied, the four exhibiting the most NK cell-mediated control of viral replication also had the fewest activating KIR and were haplotype A. Thus, the strong NK cell-mediated inhibition of viral replication is not necessary for the immunological control of HIV-1 in all ES.

* Corresponding author. Mailing address: Broadway Research Bldg., Rm. 880, Johns Hopkins University School of Medicine, 722 N. Broadway, Baltimore, MD 21205. Phone: (410) 955-7757. Fax: (443) 287-6218. E-mail: jblanks{at}jhmi.edu

{triangledown} Published ahead of print on 11 February 2009.

Journal of Virology, May 2009, p. 5028-5034, Vol. 83, No. 10
0022-538X/09/$08.00+0     doi:10.1128/JVI.02551-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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