SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection

TY - JOUR

T1 - SAMHD1 host restriction factor

T2 - a link with innate immune sensing of retrovirus infection

AU - Sze, Alexandre

AU - Olagnier, David

AU - Lin, Rongtuan

AU - van Grevenynghe, Julien

AU - Hiscott, John

N1 - © 2013.

PY - 2013/12/13

Y1 - 2013/12/13

N2 - SAMHD1 [sterile alpha motif and histidine-aspartic domain (HD) containing protein 1] is the most recent addition to a unique group of host restriction factors that limit retroviral replication at distinct stages of the viral life cycle. SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase that degrades the intracellular pool of deoxynucleoside triphosphates available during early reverse transcription. SAMHD1 activity is blocked by the Vpx accessory function present in human immunodeficiency virus type 2 and SIVsm. Mutations in SAMHD1 are associated with the autoimmune disorder Aicardi-Goutières syndrome, thus emphasizing its role in regulation of the immune response. SAMHD1 antiretroviral activity is modulated by post-translational modifications, cell-cycle-dependent functions and cytokine-mediated changes. Innate receptors that sense retroviral DNA intermediates are the focus of intense study, and recent studies have established a link among SAMHD1 restriction, innate sensing of DNA and protective immune responses. Cell-cycle-dependent regulation of SAMHD1 by phosphorylation and the increasingly broad range of viruses inhibited by SAMHD1 further emphasize the importance of these mechanisms of host restriction. This review highlights current knowledge regarding SAMHD1 regulation and its impact on innate immune signaling and retroviral restriction.

AB - SAMHD1 [sterile alpha motif and histidine-aspartic domain (HD) containing protein 1] is the most recent addition to a unique group of host restriction factors that limit retroviral replication at distinct stages of the viral life cycle. SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase that degrades the intracellular pool of deoxynucleoside triphosphates available during early reverse transcription. SAMHD1 activity is blocked by the Vpx accessory function present in human immunodeficiency virus type 2 and SIVsm. Mutations in SAMHD1 are associated with the autoimmune disorder Aicardi-Goutières syndrome, thus emphasizing its role in regulation of the immune response. SAMHD1 antiretroviral activity is modulated by post-translational modifications, cell-cycle-dependent functions and cytokine-mediated changes. Innate receptors that sense retroviral DNA intermediates are the focus of intense study, and recent studies have established a link among SAMHD1 restriction, innate sensing of DNA and protective immune responses. Cell-cycle-dependent regulation of SAMHD1 by phosphorylation and the increasingly broad range of viruses inhibited by SAMHD1 further emphasize the importance of these mechanisms of host restriction. This review highlights current knowledge regarding SAMHD1 regulation and its impact on innate immune signaling and retroviral restriction.

KW - Autoimmune Diseases of the Nervous System/genetics

KW - DNA, Viral/genetics

KW - Gene Expression Regulation/immunology

KW - HIV Infections/immunology

KW - HIV-1/immunology

KW - HIV-2/immunology

KW - Host-Pathogen Interactions

KW - Humans

KW - Immunity, Innate/immunology

KW - Models, Immunological

KW - Monomeric GTP-Binding Proteins/chemistry

KW - Nervous System Malformations/genetics

KW - Retroviridae/immunology

KW - Retroviridae Infections/immunology

KW - SAM Domain and HD Domain-Containing Protein 1

KW - Signal Transduction

KW - Structure-Activity Relationship

KW - Viral Proteins/genetics

KW - Viral Regulatory and Accessory Proteins/genetics

KW - Virus Replication/immunology

U2 - 10.1016/j.jmb.2013.10.022

DO - 10.1016/j.jmb.2013.10.022

M3 - Review

C2 - 24161438

SN - 0022-2836

VL - 425

SP - 4981

EP - 4994

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 24

ER -