title: Unmasking immune sensing of retroviruses: interplay between innate sensors and host effectors.
abstract: Retroviruses can selectively trigger an array of innate immune responses through various PRR. The identification and the characterization of the molecular basis of retroviral DNA sensing by the DNA sensors IFI16 and cGAS has been one of the most exciting developments in viral immunology in recent years. DNA sensing by these cytosolic sensors not only leads to the initiation of the type I interferon (IFN) antiviral response and the induction of the inflammatory response, but also triggers cell death mechanisms including pyroptosis and apoptosis in retrovirus-infected cells, thereby providing important insights into the pathophysiology of chronic retroviral infection. Host restriction factors such as SAMHD1 and Trex1 play important roles in regulating innate immune sensing, and have led to the idea that innate immune defense and host restriction actually converge at different levels to determine the outcome of retroviral infection. In this review, we discuss the sensing of retroviruses by cytosolic DNA sensors, the relevance of host factors during retroviral infection, and the interplay between host factors and the innate antiviral response in different cell types, within the context of two human pathogenic retroviruses - human immunodeficiency virus (HIV-1) and human T cell-leukemia virus type I (HTLV-1).
authors.affiliation: Vaccine & Gene Therapy Institute of Florida, 9801 Discovery Way, Port Saint Lucie, FL 34987, USA.
authors.forename: Nadine
authors.initials: N
authors.lastname: van Montfoort
authors.affiliation: Vaccine & Gene Therapy Institute of Florida, 9801 Discovery Way, Port Saint Lucie, FL 34987, USA.
authors.forename: David
authors.initials: D
authors.lastname: Olagnier
authors.affiliation: Vaccine & Gene Therapy Institute of Florida, 9801 Discovery Way, Port Saint Lucie, FL 34987, USA. Electronic address: jhiscott@vgtifl.org.
authors.forename: John
authors.initials: J
authors.lastname: Hiscott
mesh_terms: D000818:Animals; D005090:Exodeoxyribonucleases / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015490:HTLV-I Infections / Q000235:genetics / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D009713:Nucleotidyltransferases / Q000235:genetics / Q000276:immunology; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology; D000076106:SAM Domain and HD Domain-Containing Protein 1; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D005090:Exodeoxyribonucleases; D020559:Monomeric GTP-Binding Proteins; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; D010750:Phosphoproteins; D000076106:SAM Domain and HD Domain-Containing Protein 1; C076700:IFI16 protein, human; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase; C429526:three prime repair exonuclease 1; C484280:SAMHD1 protein, human
keywords: HIV-1; HTLV-1; Host restriction factors; Innate immune sensing; Retroviruses; SAMHD1; Trex1, STING, cGAS, cGAMP, interferon