The macrophage: a therapeutic target in HIV-1 infection

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Human immunodeficiency virus (HIV) is still a serious global health concern responsible for more than 25 million deaths in last three decades. More than 34 million people are living with HIV infection. Macrophages and CD4+ T cells are the principal targets of HIV-1. The pathogenesis of HIV-1 takes different routes in macrophages and CD4+ T cells. Macrophages are resistant to the cytopathic effect of HIV-1 and produce virus for longer periods of time. In addition, macrophages being present in every organ system thus can disseminate virus to the different anatomical sites leading to the formation of viral sanctuaries. Complete cure of HIV-1 needs better understanding of viral pathogenesis in these reservoirs and implementation of knowledge into robust therapeutic products. In this review we will focus on the unique relationship between HIV-1 and macrophages. Furthermore, we will describe how successful antiretroviral therapy (ART) is in suppressing HIV and novel molecular and cellular strategies against HIV-1 in macrophages.

Related collections

Most cited references 145

Record: found
Abstract: found
Article: not found

Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu.

Stuart J D Neil, Trinity Zang, Paul D. Bieniasz (2008)

Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV-1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-alpha, and it consists of protein-based tethers, which we term 'tetherins', that cause retention of fully formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, we identify CD317 (also called BST2 or HM1.24), a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukaemia virus particle release. Furthermore, in cells where HIV-1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces and, after endocytosis, in CD317-positive compartments. Vpu co-localized with CD317 and inhibited these effects. Inhibition of Vpu function and consequent mobilization of tetherin's antiviral activity is a potential therapeutic strategy in HIV/AIDS.

0 comments Cited 687 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

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.

0 comments Cited 530 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome.

R Koup, J. T. Safrit, Y Cao … (1994)

Virologic and immunologic studies were performed on five patients presenting with primary human immunodeficiency virus type 1 (HIV-1) infection. CD8+ cytotoxic T lymphocyte (CTL) precursors specific for cells expressing antigens of HIV-1 Gag, Pol, and Env were detected at or within 3 weeks of presentation in four of the five patients and were detected in all five patients by 3 to 6 months after presentation. The one patient with an absent initial CTL response had prolonged symptoms, persistent viremia, and low CD4+ T-cell count. Neutralizing antibody activity was absent at the time of presentation in all five patients. These findings suggest that cellular immunity is involved in the initial control of virus replication in primary HIV-1 infection and indicate a role for CTL in protective immunity to HIV-1 in vivo.

0 comments Cited 319 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Amit Kumar: amit.aiims2005@gmail.com

Georges Herbein: georges.herbein@univ-fcomte.fr

Journal

Journal ID (nlm-ta): Mol Cell Ther

Journal ID (iso-abbrev): Mol Cell Ther

Title: Molecular and cellular therapies

Publisher: BioMed Central (London )

ISSN (Electronic): 2052-8426

Publication date (Electronic): 2 April 2014

Publication date PMC-release: 2 April 2014

Publication date Collection: 2014

Volume: 2

Electronic Location Identifier: 10

Affiliations

[ ]Department of Virology, UPRES EA4266 Pathogens & Inflammation, University of Franche-Comte, SFR FED 4234, F-25030 Besançon, France

[ ]Department of Virology, Hôpital Saint-Jacques, CHRU Besançon, 2 place Saint-Jacques, F-25030 Besançon cedex, France

Article

Publisher ID: 13

DOI: 10.1186/2052-8426-2-10

PMC ID: 4452058

PubMed ID: 26056579

SO-VID: 872b329e-c6ee-4881-8a5c-9ab9c44684b3

License:

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.