Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes

Balthasar A. Heesters; Madelene Lindqvist; Parsia A. Vagefi; Eileen P. Scully; Frank A. Schildberg; Marcus Altfeld; Bruce D. Walker; Daniel E. Kaufmann; Michael C. Carroll

doi:10.1371/journal.ppat.1005285

Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes

Balthasar A. Heesters, Madelene Lindqvist, Parsia A. Vagefi, Eileen P. Scully, Frank A. Schildberg, Marcus Altfeld, Bruce D. Walker, Daniel E. Kaufmann, Michael C. Carroll

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

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.

Original language	English (US)
Article number	e1005285
Journal	PLoS pathogens
Volume	11
Issue number	12
DOIs	https://doi.org/10.1371/journal.ppat.1005285
State	Published - 2015
Externally published	Yes

ASJC Scopus subject areas

Parasitology
Microbiology
Immunology
Molecular Biology
Genetics
Virology

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10.1371/journal.ppat.1005285

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title = "Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes",

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.",

author = "Heesters, {Balthasar A.} and Madelene Lindqvist and Vagefi, {Parsia A.} and Scully, {Eileen P.} and Schildberg, {Frank A.} and Marcus Altfeld and Walker, {Bruce D.} and Kaufmann, {Daniel E.} and Carroll, {Michael C.}",

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doi = "10.1371/journal.ppat.1005285",

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AU - Heesters, Balthasar A.

AU - Lindqvist, Madelene

AU - Vagefi, Parsia A.

AU - Scully, Eileen P.

AU - Schildberg, Frank A.

AU - Altfeld, Marcus

AU - Walker, Bruce D.

AU - Kaufmann, Daniel E.

AU - Carroll, Michael C.

PY - 2015

Y1 - 2015

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AB - 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.

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Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes

Abstract

ASJC Scopus subject areas

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