A Novel Assay to Measure the Magnitude of the Inducible Viral Reservoir in HIV-infected Individuals.

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Abstract

Quantifying latently infected cells is critical to evaluate the efficacy of therapeutic strategies aimed at reducing the size of the long-lived viral reservoir, but the low frequency of these cells makes this very challenging.

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Most cited references 50

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Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy.

J. Gallant, R Brookmeyer, J Margolick … (1998)

The hypothesis that quiescent CD4+ T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus-type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes. The frequency of resting CD4+ T cells harboring latent HIV-1 was low, 0.2 to 16.4 per 10(6) cells, and, in cross-sectional analysis, did not decrease with increasing time on therapy. The recovered viruses generally did not show mutations associated with resistance to the relevant antiretroviral drugs. This reservoir of nonevolving latent virus in resting CD4+ T cells should be considered in deciding whether to terminate treatment in patients who respond to HAART.

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Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.

D Ho, A Neumann, A S Perelson … (1995)

Treatment of infected patients with ABT-538, an inhibitor of the protease of human immunodeficiency virus type 1 (HIV-1), causes plasma HIV-1 levels to decrease exponentially (mean half-life, 2.1 +/- 0.4 days) and CD4 lymphocyte counts to rise substantially. Minimum estimates of HIV-1 production and clearance and of CD4 lymphocyte turnover indicate that replication of HIV-1 in vivo is continuous and highly productive, driving the rapid turnover of CD4 lymphocytes.

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Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection.

Tae-Wook Chun, Lucy Carruth, Diana Finzi … (1997)

The capacity of HIV-1 to establish latent infection of CD4+ T cells may allow viral persistence despite immune responses and antiretroviral therapy. Measurements of infectious virus and viral RNA in plasma and of infectious virus, viral DNA and viral messenger RNA species in infected cells all suggest that HIV-1 replication continues throughout the course of infection. Uncertainty remains over what fraction of CD4+ T cells are infected and whether there are latent reservoirs for the virus. We show here that during the asymptomatic phase of infection there is an extremely low total body load of latently infected resting CD4+ T cells with replication-competent integrated provirus (<10(7) cells). The most prevalent form of HIV-1 DNA in resting and activated CD4+ T cells is a full-length, linear, unintegrated form that is not replication competent. The infection progresses even though at any given time in the lymphoid tissues integrated HIV-1 DNA is present in only a minute fraction of the susceptible populations, including resting and activated CD4+ T cells and macrophages.

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Author and article information

Journal

Journal ID (iso-abbrev): EBioMedicine

Title: EBioMedicine

Publisher: Elsevier BV

ISSN: 2352-3964

ISSN (Print): 2352-3964

Publication date (Electronic): Aug 2015

Volume: 2

Issue: 8

Affiliations

[1 ] Vaccine and Gene Therapy Institute Florida, Port St. Lucie, FL, USA.

[2 ] University of California San Diego, La Jolla, California and Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.

[3 ] Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.

[4 ] Centre for Virus Research, Westmead Millennium Institute, Westmead, Australia ; Sydney Medical School, University of Sydney, Sydney, Australia.

[5 ] Department of Medicine, University of California San Francisco, San Francisco, CA, USA.

[6 ] Infectious Disease, Merck Research Laboratories, West Point, PA, USA.

Article

Publisher Item ID: S2352-3964(15)30048-7

DOI: 10.1016/j.ebiom.2015.06.019

PMC ID: 4563128

PubMed ID: 26425694

SO-VID: e94428e8-1d2f-4340-b42c-6aa654a87273

History

Keywords: Eradication,HIV,Inducible virus,Latency,Multiply spliced RNA,Reservoir,TILDA

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Keywords: Eradication, HIV, Inducible virus, Latency, Multiply spliced RNA, Reservoir, TILDA

A Novel Assay to Measure the Magnitude of the Inducible Viral Reservoir in HIV-infected Individuals.

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Abstract

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Most cited references 50

Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy.

Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.

Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection.

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