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Innate immune sensing of HIV-1 infection

Jakobsen, Martin R.; Olagnier, David; Hiscott, John

Current Opinion in HIV and AIDS: March 2015 - Volume 10 - Issue 2 - p 96–102
doi: 10.1097/COH.0000000000000129
GENOMICS IN HIV INFECTION: Edited by Amalio Telenti

Purpose of review The innate immune system plays a critical role in the control of viral infections. Although the mechanisms involved in sensing and response to viral pathogens has progressed tremendously in the last decade, an understanding of the innate antiviral response to human retroviruses lagged behind. Recent studies now demonstrate that human retroviruses such as human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus 1 (HTLV-1) trigger a type I interferon antiviral response through novel cytosolic sensors that detect DNA intermediates of reverse transcription; in addition, these early host–pathogen interactions may trigger cell death pathways depending on the activation state of the target cell. The purpose of this review is to summarize the recent progress in the understanding of innate immune sensing of human retroviruses.

Recent findings Innate immune sensing of HIV-1 and HTLV-1 is influenced by the target cell phenotype, viral replicative intermediates, and host restriction factors that limit retroviral replication. Macrophages and dendritic cells detect HIV-DNA intermediates, whereas CD4+ T cells differentially sense HIV DNA depending on the level of T-cell activation. Furthermore, the structure of the viral capsid and interplay between innate DNA sensors and host restriction factors all contribute to the magnitude of the ensuing innate immune response.

Summary The interplay between HIV infection and the innate immune system has emerged as an important component of HIV pathogenesis, linked to both induction of innate immunity and stimulation of cell death mechanisms. Ultimately, an in-depth knowledge of the mechanisms of innate immune control of human retrovirus infection may facilitate the development of novel treatment strategies to control retrovirus-induced immunopathology.

aInstitute of Biomedicine, Faculty of Health, Aarhus University

bAarhus Research Centre of Innate Immunology, Aarhus, Denmark

cVaccine and Gene Therapy Institute of Florida, Port Saint Lucie, Florida, USA

Correspondence to Martin R. Jakobsen, Faculty of Health, Institute of Biomedicine, Aarhus University, Wilhelm Meyers Alle 4, 8000 Aarhus C, Denmark. Tel: +45 8716 7846; e-mail: mrj@biomed.au.dk

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