Safeguard against DNA sensing: the role of TREX1 in HIV-1 infection and autoimmune diseases.

Maroof Hasan,Nan Yan

doi:10.3389/fmicb.2014.00193

Abstract

Innate immune recognition is crucial for host responses against viral infections, including infection by human immunodeficiency virus 1 (HIV-1). Human cells detect such invading pathogens with a collection of pattern recognition receptors that activate the production of antiviral proteins, such as the cytokine interferon-type I, to initiate antiviral responses immediately as well as the adaptive immune response for long-term protection. To establish infection in the host, many viruses have thus evolved strategies for subversion of these mechanisms of innate immunity. For example, acute infection by HIV-1 and other retroviruses have long been thought to be non-immunogenic, signifying suppression of host defenses by these pathogens. Studies in the past few years have begun to uncover a multifaceted scheme of how HIV-1 evades innate immune detection, especially of its DNA, by exploiting host proteins. This review will discuss the host mechanisms of HIV-1 DNA sensing and viral immune evasion, with a particular focus on TREX1, three prime repair exonuclease 1, a host 3′ exonuclease (also known as DNase III).

Highlights

THE INTERFERON RESPONSE TO HIV DNA Human immunodeficiency virus (HIV) enters T cells and macrophages by first interacting with host receptor CD4 with co-receptor chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor 4 (CXCR4) on the target cell plasma membrane, triggering viral envelope fusion
The HIV DNA is sensed by binding to cGAMP synthase, which synthesizes the unique second messenger dinucleotide cyclic GMP-AMP that binds to stimulator of interferon genes (STING) to activate downstream IFN signaling (Gao et al, 2013; Figure 1A)
Extensive effort in the past two decades provided us with incredible details on human immunodeficiency virus 1 (HIV-1) virology, life cycle, interactions with host factors, and antagonism of host intrinsic restriction factors with accessory proteins (Goff, 2007)

Summary

Introduction

THE INTERFERON RESPONSE TO HIV DNA Human immunodeficiency virus (HIV) enters T cells and macrophages by first interacting with host receptor CD4 with co-receptor chemokine (C-C motif) receptor 5 (CCR5) or chemokine (C-X-C motif) receptor 4 (CXCR4) on the target cell plasma membrane, triggering viral envelope fusion. The HIV-encoded cytosolic DNA produced by reverse transcription does not trigger a cell-autonomous interferon (IFN) or inflammatory response in activated CD4 T cells and macrophages, its primary targets (Goldfeld et al, 1991; Yan et al, 2010).

Results

Conclusion