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PLoS Pathog. 2015 Dec 1;11(12):e1005285. doi: 10.1371/journal.ppat.1005285. eCollection 2015 Dec.

Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes.

Author information

1
Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
2
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
3
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
4
Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts, United States of America.
5
Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, California, United States of America.
6
Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
7
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America.
8
Department of Viral Immunology, Leibniz Institute for Experimental Virology, Hamburg, Germany.
9
Centre de Recherché du CHUM; Department of Medicine, Université de Montréal, Montreal, Quebec, Canada.
10
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, United States of America.

Abstract

Despite the success of antiretroviral therapy (ART), it does not cure Human Immunodeficiency Virus (HIV) and discontinuation results in viral rebound. Follicular dendritic cells (FDC) are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4 T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans.

PMID:
26623655
PMCID:
PMC4666623
DOI:
10.1371/journal.ppat.1005285
[Indexed for MEDLINE]
Free PMC Article

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