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Journal of Virology, June 2008, p. 5548-5561, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.00124-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Characterization of the Follicular Dendritic Cell Reservoir of Human Immunodeficiency Virus Type 1 ^,

Brandon F. Keele,^1, Loubna Tazi,² Suzanne Gartner,³ Yiling Liu,³ Trever B. Burgon,^1, Jacob D. Estes,^1,¶ Tyler C. Thacker,^1,|| Keith A. Crandall,² Justin C. McArthur,³ and Gregory F. Burton^1*

Department of Chemistry and Biochemistry,¹ Department of Biology, Brigham Young University, Provo, Utah 84602,² Department of Neurology, Johns Hopkins University, Baltimore, Maryland 21287³

Received 17 January 2008/ Accepted 24 March 2008

Throughout the natural course of human immunodeficiency virus (HIV) infection, follicular dendritic cells (FDCs) trap and retain large quantities of particle-associated HIV RNA in the follicles of secondary lymphoid tissue. We have previously found that murine FDCs in vivo could maintain trapped virus particles in an infectious state for at least 9 months. Here we sought to determine whether human FDCs serve as an HIV reservoir, based on the criteria that virus therein must be replication competent, genetically diverse, and archival in nature. We tested our hypothesis using postmortem cells and tissues obtained from three HIV-infected subjects and antemortem blood samples obtained from one of these subjects. Replication competence was determined using coculture, while genetic diversity and the archival nature of virus were established using phylogenetic and population genetics methods. We found that FDC-trapped virus was replication competent and demonstrated greater genetic diversity than that of virus found in most other tissues and cells. Antiretrovirus-resistant variants that were not present elsewhere were also detected on FDCs. Furthermore, genetic similarity was observed between FDC-trapped HIV and viral species recovered from peripheral blood mononuclear cells obtained 21 and 22 months antemortem, but was not present in samples obtained 4 and 18 months prior to the patient's death, indicating that FDCs can archive HIV. These data indicate that FDCs represent a significant reservoir of infectious and diverse HIV, thereby providing a mechanism for viral persistence for months to years.

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* Corresponding author. Mailing address: Rm. C211A BNSN, Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602. Phone: (801) 422-4917. Fax: (801) 422-0153. E-mail: greg_burton{at}byu.edu

Published ahead of print on 2 April 2008.

Supplemental material for this article may be found at http://jvi.asm.org/.

Present address: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-0024.

Present address: Department Microbiology and Immunology, Stanford University, Stanford, CA 94305.

^¶ Present address: AIDS Vaccine Program, NCI-Frederick, Fort Detrick Campus, Frederick, MD 21702.

^|| Present address: Tuberculosis Research Unit, USDA Agricultural Research Service, Ames, IA 50201.

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Journal of Virology, June 2008, p. 5548-5561, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.00124-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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