A proteomics perspective on viral DNA sensors in host defense and viral immune evasion mechanisms.
The sensing of viral DNA is an essential step of cellular immune response to infections with DNA viruses. These human pathogens are spread worldwide, triggering a wide range of virus-induced diseases, and are associated with high levels of morbidity and mortality. Despite similarities between DNA molecules, mammalian cells have the remarkable ability to distinguish viral DNA from their own DNA. This detection is carried out by specialized antiviral proteins, called DNA sensors. These sensors bind to foreign DNA to activate downstream immune signaling pathways and alert neighboring cells by eliciting the expression of antiviral cytokines. The sensing of viral DNA was shown to occur both in the cytoplasm and in the nucleus of infected cells, disproving the notion that sensing occurred by simple spatial separation of viral and host DNA. A number of omic approaches, in particular, mass-spectrometry-based proteomic methods, have significantly contributed to the constantly evolving field of viral DNA sensing. Here, we review the impact of omic methods on the identification of viral DNA sensors, as well as on the characterization of mechanisms involved in host defense or viral immune evasion.
Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
Marni S
MS
Crow
Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
Aaron
A
Javitt
Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA. Electronic address: icristea@princeton.edu.
Ileana M
IM
Cristea
D000818:Animals; D003593:Cytoplasm / Q000235:genetics / Q000821:virology; D004279:DNA, Viral / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D008322:Mammals / Q000276:immunology; D013058:Mass Spectrometry / Q000379:methods; D009687:Nuclear Proteins / Q000276:immunology / Q000378:metabolism; D009713:Nucleotidyltransferases / Q000276:immunology / Q000378:metabolism; D010750:Phosphoproteins / Q000276:immunology / Q000378:metabolism; D060066:Protein Interaction Maps; D011506:Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015398:Signal Transduction / Q000276:immunology; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
D004279:DNA, Viral; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; D010750:Phosphoproteins; D011506:Proteins; C076700:IFI16 protein, human; C578390:cGAS protein, human; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
IFI16; immune response; proteomics; viral DNA sensing; virus–host interactions