• This record comes from PubMed

The Interplay between Viruses and Host DNA Sensors

. 2022 Mar 23 ; 14 (4) : . [epub] 20220323

Language English Country Switzerland Media electronic

Document type Journal Article, Review, Research Support, Non-U.S. Gov't

DNA virus infections are often lifelong and can cause serious diseases in their hosts. Their recognition by the sensors of the innate immune system represents the front line of host defence. Understanding the molecular mechanisms of innate immunity responses is an important prerequisite for the design of effective antivirotics. This review focuses on the present state of knowledge surrounding the mechanisms of viral DNA genome sensing and the main induced pathways of innate immunity responses. The studies that have been performed to date indicate that herpesviruses, adenoviruses, and polyomaviruses are sensed by various DNA sensors. In non-immune cells, STING pathways have been shown to be activated by cGAS, IFI16, DDX41, or DNA-PK. The activation of TLR9 has mainly been described in pDCs and in other immune cells. Importantly, studies on herpesviruses have unveiled novel participants (BRCA1, H2B, or DNA-PK) in the IFI16 sensing pathway. Polyomavirus studies have revealed that, in addition to viral DNA, micronuclei are released into the cytosol due to genotoxic stress. Papillomaviruses, HBV, and HIV have been shown to evade DNA sensing by sophisticated intracellular trafficking, unique cell tropism, and viral or cellular protein actions that prevent or block DNA sensing. Further research is required to fully understand the interplay between viruses and DNA sensors.

See more in PubMed

Saxena M., Yeretssian G. NOD-Like Receptors: Master Regulators of Inflammation and Cancer. Front. Immunol. 2014;5:327. doi: 10.3389/fimmu.2014.00327. PubMed DOI PMC

Drouin M., Saenz J., Chiffoleau E. C-Type Lectin-Like Receptors: Head or Tail in Cell Death Immunity. Front. Immunol. 2020;11:251. doi: 10.3389/fimmu.2020.00251. PubMed DOI PMC

Kawai T., Akira S. The Roles of TLRs, RLRs and NLRs in Pathogen Recognition. Int. Immunol. 2009;21:317–337. doi: 10.1093/intimm/dxp017. PubMed DOI PMC

Oliveira Mann C.C., Hornung V. Molecular Mechanisms of Nonself Nucleic Acid Recognition by the Innate Immune System. Eur. J. Immunol. 2021;51:1897–1910. doi: 10.1002/eji.202049116. PubMed DOI

Rehwinkel J., Gack M.U. RIG-I-like Receptors: Their Regulation and Roles in RNA Sensing. Nat. Rev. Immunol. 2020;20:537–551. doi: 10.1038/s41577-020-0288-3. PubMed DOI PMC

Caneparo V., Landolfo S., Gariglio M., De Andrea M. The Absent in Melanoma 2-Like Receptor IFN-Inducible Protein 16 as an Inflammasome Regulator in Systemic Lupus Erythematosus: The Dark Side of Sensing Microbes. Front. Immunol. 2018;9:1180. doi: 10.3389/fimmu.2018.01180. PubMed DOI PMC

Bürckstümmer T., Baumann C., Blüml S., Dixit E., Dürnberger G., Jahn H., Planyavsky M., Bilban M., Colinge J., Bennett K.L., et al. An Orthogonal Proteomic-Genomic Screen Identifies AIM2 as a Cytoplasmic DNA Sensor for the Inflammasome. Nat. Immunol. 2009;10:266–272. doi: 10.1038/ni.1702. PubMed DOI

Howard T.R., Crow M.S., Greco T.M., Lum K.K., Li T., Cristea I.M. The DNA Sensor IFIX Drives Proteome Alterations To Mobilize Nuclear and Cytoplasmic Antiviral Responses, with Its Acetylation Acting as a Localization Toggle. mSystems. 2021;6:e00397-21. doi: 10.1128/mSystems.00397-21. PubMed DOI PMC

Unterholzner L., Keating S.E., Baran M., Horan K.A., Jensen S.B., Sharma S., Sirois C.M., Jin T., Latz E., Xiao T.S., et al. IFI16 Is an Innate Immune Sensor for Intracellular DNA. Nat. Immunol. 2010;11:997–1004. doi: 10.1038/ni.1932. PubMed DOI PMC

Diner B.A., Li T., Greco T.M., Crow M.S., Fuesler J.A., Wang J., Cristea I.M. The Functional Interactome of PYHIN Immune Regulators Reveals IFIX Is a Sensor of Viral DNA. Mol. Syst. Biol. 2015;11:787. doi: 10.15252/msb.20145808. PubMed DOI PMC

Chen W., Yu S.-X., Zhou F.-H., Zhang X.-J., Gao W.-Y., Li K.-Y., Liu Z.-Z., Han W.-Y., Yang Y.-J. DNA Sensor IFI204 Contributes to Host Defense Against Staphylococcus Aureus Infection in Mice. Front. Immunol. 2019;10:474. doi: 10.3389/fimmu.2019.00474. PubMed DOI PMC

Takaoka A., Wang Z., Choi M.K., Yanai H., Negishi H., Ban T., Lu Y., Miyagishi M., Kodama T., Honda K., et al. DAI (DLM-1/ZBP1) Is a Cytosolic DNA Sensor and an Activator of Innate Immune Response. Nature. 2007;448:501–505. doi: 10.1038/nature06013. PubMed DOI

Wu J., Sun L., Chen X., Du F., Shi H., Chen C., Chen Z.J. Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. Science. 2013;339:826–830. doi: 10.1126/science.1229963. PubMed DOI PMC

Sun L., Wu J., Du F., Chen X., Chen Z.J. Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway. Science. 2013;339:786–791. doi: 10.1126/science.1232458. PubMed DOI PMC

Zhang Z., Yuan B., Bao M., Lu N., Kim T., Liu Y.-J. The Helicase DDX41 Senses Intracellular DNA Mediated by the Adaptor STING in Dendritic Cells. Nat. Immunol. 2011;12:959–965. doi: 10.1038/ni.2091. PubMed DOI PMC

Kim T., Pazhoor S., Bao M., Zhang Z., Hanabuchi S., Facchinetti V., Bover L., Plumas J., Chaperot L., Qin J., et al. Aspartate-Glutamate-Alanine-Histidine Box Motif (DEAH)/RNA Helicase A Helicases Sense Microbial DNA in Human Plasmacytoid Dendritic Cells. Proc. Natl. Acad. Sci. USA. 2010;107:15181–15186. doi: 10.1073/pnas.1006539107. PubMed DOI PMC

Ng Y.C., Chung W.-C., Kang H.-R., Cho H.-J., Park E.-B., Kang S.-J., Song M.J. A DNA-Sensing–Independent Role of a Nuclear RNA Helicase, DHX9, in Stimulation of NF-ΚB–Mediated Innate Immunity against DNA Virus Infection. Nucleic Acids Res. 2018;46:9011–9026. doi: 10.1093/nar/gky742. PubMed DOI PMC

Chiu Y.-H., MacMillan J.B., Chen Z.J. RNA Polymerase III Detects Cytosolic DNA and Induces Type I Interferons through the RIG-I Pathway. Cell. 2009;138:576–591. doi: 10.1016/j.cell.2009.06.015. PubMed DOI PMC

Kondo T., Kobayashi J., Saitoh T., Maruyama K., Ishii K.J., Barber G.N., Komatsu K., Akira S., Kawai T. DNA Damage Sensor MRE11 Recognizes Cytosolic Double-Stranded DNA and Induces Type I Interferon by Regulating STING Trafficking. Proc. Natl. Acad. Sci. USA. 2013;110:2969–2974. doi: 10.1073/pnas.1222694110. PubMed DOI PMC

Ferguson B.J., Mansur D.S., Peters N.E., Ren H., Smith G.L. DNA-PK Is a DNA Sensor for IRF-3-Dependent Innate Immunity. eLife. 2012;1:e00047. doi: 10.7554/eLife.00047. PubMed DOI PMC

Sui H., Hao M., Chang W., Imamichi T. The Role of Ku70 as a Cytosolic DNA Sensor in Innate Immunity and Beyond. Front. Cell. Infect. Microbiol. 2021;11:761983. doi: 10.3389/fcimb.2021.761983. PubMed DOI PMC

Johnstone R.W., Wei W., Greenway A., Trapani J.A. Functional Interaction between P53 and the Interferon-Inducible Nucleoprotein IFI 16. Oncogene. 2000;19:6033–6042. doi: 10.1038/sj.onc.1204005. PubMed DOI

Johnstone R.W., Kerry J.A., Trapani J.A. The Human Interferon-Inducible Protein, IFI 16, Is a Repressor of Transcription. J. Biol. Chem. 1998;273:17172–17177. doi: 10.1074/jbc.273.27.17172. PubMed DOI

Roy A., Ghosh A., Kumar B., Chandran B. IFI16, a Nuclear Innate Immune DNA Sensor, Mediates Epigenetic Silencing of Herpesvirus Genomes by Its Association with H3K9 Methyltransferases SUV39H1 and GLP. eLife. 2019;8:e49500. doi: 10.7554/eLife.49500. PubMed DOI PMC

Johnson K.E., Bottero V., Flaherty S., Dutta S., Singh V.V., Chandran B. IFI16 Restricts HSV-1 Replication by Accumulating on the HSV-1 Genome, Repressing HSV-1 Gene Expression, and Directly or Indirectly Modulating Histone Modifications. PLoS Pathog. 2014;10:e1004503. doi: 10.1371/journal.ppat.1004503. PubMed DOI PMC

Jiang H., Xue X., Panda S., Kawale A., Hooy R.M., Liang F., Sohn J., Sung P., Gekara N.O. Chromatin-bound cGAS Is an Inhibitor of DNA Repair and Hence Accelerates Genome Destabilization and Cell Death. EMBO J. 2019;38:e102718. doi: 10.15252/embj.2019102718. PubMed DOI PMC

Liu H., Zhang H., Wu X., Ma D., Wu J., Wang L., Jiang Y., Fei Y., Zhu C., Tan R., et al. Nuclear CGAS Suppresses DNA Repair and Promotes Tumorigenesis. Nature. 2018;563:131–136. doi: 10.1038/s41586-018-0629-6. PubMed DOI

Zierhut C., Yamaguchi N., Paredes M., Luo J.-D., Carroll T., Funabiki H. The Cytoplasmic DNA Sensor CGAS Promotes Mitotic Cell Death. Cell. 2019;178:302–315.e23. doi: 10.1016/j.cell.2019.05.035. PubMed DOI PMC

Cui S., Yu Q., Chu L., Cui Y., Ding M., Wang Q., Wang H., Chen Y., Liu X., Wang C. Nuclear CGAS Functions Non-Canonically to Enhance Antiviral Immunity via Recruiting Methyltransferase Prmt5. Cell Rep. 2020;33:108490. doi: 10.1016/j.celrep.2020.108490. PubMed DOI

Ablasser A., Goldeck M., Cavlar T., Deimling T., Witte G., Röhl I., Hopfner K.-P., Ludwig J., Hornung V. CGAS Produces a 2′-5′-Linked Cyclic Dinucleotide Second Messenger That Activates STING. Nature. 2013;498:380–384. doi: 10.1038/nature12306. PubMed DOI PMC

Sui H., Zhou M., Imamichi H., Jiao X., Sherman B.T., Lane H.C., Imamichi T. STING Is an Essential Mediator of the Ku70-Mediated Production of IFN-Λ1 in Response to Exogenous DNA. Sci. Signal. 2017;10:eaah5054. doi: 10.1126/scisignal.aah5054. PubMed DOI

Burleigh K., Maltbaek J.H., Cambier S., Green R., Gale M., James R.C., Stetson D.B. Human DNA-PK Activates a STING-Independent DNA Sensing Pathway. Sci. Immunol. 2020;5:eaba4219. doi: 10.1126/sciimmunol.aba4219. PubMed DOI PMC

Yang P., An H., Liu X., Wen M., Zheng Y., Rui Y., Cao X. The Cytosolic Nucleic Acid Sensor LRRFIP1 Mediates the Production of Type I Interferon via a β-Catenin-Dependent Pathway. Nat. Immunol. 2010;11:487–494. doi: 10.1038/ni.1876. PubMed DOI

Liu Y., Zou Z., Zhu B., Hu Z., Zeng P., Wu L. LRRFIP1 Inhibits Hepatitis C Virus Replication by Inducing Type I Interferon in Hepatocytes. Hepat. Mon. 2015;15:e28473. doi: 10.5812/hepatmon.15(5)2015.28473. PubMed DOI PMC

Rathinam V.A.K., Sharma S., Fitzgerald K.A. Catenin’ on to Nucleic Acid Sensing. Nat. Immunol. 2010;11:466–468. doi: 10.1038/ni0610-466. PubMed DOI

Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., Matsumoto M., Hoshino K., Wagner H., Takeda K., et al. A Toll-like Receptor Recognizes Bacterial DNA. Nature. 2000;408:740–745. doi: 10.1038/35047123. PubMed DOI

Kadowaki N., Ho S., Antonenko S., de Waal Malefyt R., Kastelein R.A., Bazan F., Liu Y.-J. Subsets of Human Dendritic Cell Precursors Express Different Toll-like Receptors and Respond to Different Microbial Antigens. J. Exp. Med. 2001;194:863–870. doi: 10.1084/jem.194.6.863. PubMed DOI PMC

Hornung V., Rothenfusser S., Britsch S., Krug A., Jahrsdörfer B., Giese T., Endres S., Hartmann G. Quantitative Expression of Toll-Like Receptor 1–10 MRNA in Cellular Subsets of Human Peripheral Blood Mononuclear Cells and Sensitivity to CpG Oligodeoxynucleotides. J. Immunol. 2002;168:4531–4537. doi: 10.4049/jimmunol.168.9.4531. PubMed DOI

Botos I., Segal D.M., Davies D.R. The Structural Biology of Toll-like Receptors. Structure. 2011;19:447–459. doi: 10.1016/j.str.2011.02.004. PubMed DOI PMC

Avalos A.M., Kirak O., Oelkers J.M., Pils M.C., Kim Y.-M., Ottinger M., Jaenisch R., Ploegh H.L., Brinkmann M.M. Cell-Specific TLR9 Trafficking in Primary APCs of Transgenic TLR9-GFP Mice. J. Immunol. 2013;190:695–702. doi: 10.4049/jimmunol.1202342. PubMed DOI PMC

Chockalingam A., Brooks J.C., Cameron J.L., Blum L.K., Leifer C.A. TLR9 Traffics through the Golgi Complex to Localize to Endolysosomes and Respond to CpG DNA. Immunol. Cell Biol. 2009;87:209–217. doi: 10.1038/icb.2008.101. PubMed DOI PMC

Kagan J.C., Barton G.M. Emerging Principles Governing Signal Transduction by Pattern-Recognition Receptors. Cold Spring Harb. Perspect. Biol. 2014;7:a016253. doi: 10.1101/cshperspect.a016253. PubMed DOI PMC

Kumar H., Kawai T., Akira S. Toll-like Receptors and Innate Immunity. Biochem. Biophys. Res. Commun. 2009;388:621–625. doi: 10.1016/j.bbrc.2009.08.062. PubMed DOI

Ohto U., Ishida H., Shibata T., Sato R., Miyake K., Shimizu T. Toll-like Receptor 9 Contains Two DNA Binding Sites That Function Cooperatively to Promote Receptor Dimerization and Activation. Immunity. 2018;48:649–658.e4. doi: 10.1016/j.immuni.2018.03.013. PubMed DOI

Latz E., Verma A., Visintin A., Gong M., Sirois C.M., Klein D.C.G., Monks B.G., McKnight C.J., Lamphier M.S., Duprex W.P., et al. Ligand-Induced Conformational Changes Allosterically Activate Toll-like Receptor 9. Nat. Immunol. 2007;8:772–779. doi: 10.1038/ni1479. PubMed DOI

Häcker H., Redecke V., Blagoev B., Kratchmarova I., Hsu L.-C., Wang G.G., Kamps M.P., Raz E., Wagner H., Häcker G., et al. Specificity in Toll-like Receptor Signalling through Distinct Effector Functions of TRAF3 and TRAF6. Nature. 2006;439:204–207. doi: 10.1038/nature04369. PubMed DOI

Kawai T., Sato S., Ishii K.J., Coban C., Hemmi H., Yamamoto M., Terai K., Matsuda M., Inoue J., Uematsu S., et al. Interferon-α Induction through Toll-like Receptors Involves a Direct Interaction of IRF7 with MyD88 and TRAF6. Nat. Immunol. 2004;5:1061–1068. doi: 10.1038/ni1118. PubMed DOI

Marongiu L., Gornati L., Artuso I., Zanoni I., Granucci F. Below the Surface: The Inner Lives of TLR4 and TLR9. J. Leukoc. Biol. 2019;106:147–160. doi: 10.1002/JLB.3MIR1218-483RR. PubMed DOI PMC

Hoshino K., Sasaki I., Sugiyama T., Yano T., Yamazaki C., Yasui T., Kikutani H., Kaisho T. Cutting Edge: Critical Role of IκB Kinase α in TLR7/9-Induced Type I IFN Production by Conventional Dendritic Cells. J.I. 2010;184:3341–3345. doi: 10.4049/jimmunol.0901648. PubMed DOI

Schmitz F., Heit A., Guggemoos S., Krug A., Mages J., Schiemann M., Adler H., Drexler I., Haas T., Lang R., et al. Interferon-Regulatory-Factor 1 Controls Toll-like Receptor 9-Mediated IFN-β Production in Myeloid Dendritic Cells. Eur. J. Immunol. 2007;37:315–327. doi: 10.1002/eji.200636767. PubMed DOI

Cridland J.A., Curley E.Z., Wykes M.N., Schroder K., Sweet M.J., Roberts T.L., Ragan M.A., Kassahn K.S., Stacey K.J. The Mammalian PYHIN Gene Family: Phylogeny, Evolution and Expression. BMC Evol. Biol. 2012;12:140. doi: 10.1186/1471-2148-12-140. PubMed DOI PMC

Zhao H., Gonzalezgugel E., Cheng L., Richbourgh B., Nie L., Liu C. The Roles of Interferon-Inducible P200 Family Members IFI16 and P204 in Innate Immune Responses, Cell Differentiation and Proliferation. Genes Dis. 2015;2:46–56. doi: 10.1016/j.gendis.2014.10.003. PubMed DOI PMC

Gray E.E., Winship D., Snyder J.M., Child S.J., Geballe A.P., Stetson D.B. The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA. Immunity. 2016;45:255–266. doi: 10.1016/j.immuni.2016.06.015. PubMed DOI PMC

Nakaya Y., Lilue J., Stavrou S., Moran E.A., Ross S.R. AIM2-Like Receptors Positively and Negatively Regulate the Interferon Response Induced by Cytosolic DNA. mBio. 2017;8:e00944-17. doi: 10.1128/mBio.00944-17. PubMed DOI PMC

Shaw N., Liu Z.-J. Role of the HIN Domain in Regulation of Innate Immune Responses. Mol. Cell. Biol. 2014;34:2–15. doi: 10.1128/MCB.00857-13. PubMed DOI PMC

Morrone S.R., Wang T., Constantoulakis L.M., Hooy R.M., Delannoy M.J., Sohn J. Cooperative Assembly of IFI16 Filaments on DsDNA Provides Insights into Host Defense Strategy. Proc. Natl. Acad. Sci. USA. 2014;111:E62–E71. doi: 10.1073/pnas.1313577111. PubMed DOI PMC

Jin T., Perry A., Jiang J., Smith P., Curry J.A., Unterholzner L., Jiang Z., Horvath G., Rathinam V.A., Johnstone R.W., et al. Structures of the HIN Domain:DNA Complexes Reveal Ligand Binding and Activation Mechanisms of the AIM2 Inflammasome and IFI16 Receptor. Immunity. 2012;36:561–571. doi: 10.1016/j.immuni.2012.02.014. PubMed DOI PMC

Jin T., Perry A., Smith P., Jiang J., Xiao T.S. Structure of the Absent in Melanoma 2 (AIM2) Pyrin Domain Provides Insights into the Mechanisms of AIM2 Autoinhibition and Inflammasome Assembly. J. Biol. Chem. 2013;288:13225–13235. doi: 10.1074/jbc.M113.468033. PubMed DOI PMC

Morrone S.R., Matyszewski M., Yu X., Delannoy M., Egelman E.H., Sohn J. Assembly-Driven Activation of the AIM2 Foreign-DsDNA Sensor Provides a Polymerization Template for Downstream ASC. Nat. Commun. 2015;6:7827. doi: 10.1038/ncomms8827. PubMed DOI PMC

Lu A., Magupalli V.G., Ruan J., Yin Q., Atianand M.K., Vos M.R., Schröder G.F., Fitzgerald K.A., Wu H., Egelman E.H. Unified Polymerization Mechanism for the Assembly of ASC-Dependent Inflammasomes. Cell. 2014;156:1193–1206. doi: 10.1016/j.cell.2014.02.008. PubMed DOI PMC

Ni X., Ru H., Ma F., Zhao L., Shaw N., Feng Y., Ding W., Gong W., Wang Q., Ouyang S., et al. New Insights into the Structural Basis of DNA Recognition by HINa and HINb Domains of IFI16. J. Mol. Cell Biol. 2016;8:51–61. doi: 10.1093/jmcb/mjv053. PubMed DOI

Fan X., Jiang J., Zhao D., Chen F., Ma H., Smith P., Unterholzner L., Xiao T.S., Jin T. Structural Mechanism of DNA Recognition by the P204 HIN Domain. Nucleic Acids Res. 2021;49:2959–2972. doi: 10.1093/nar/gkab076. PubMed DOI PMC

Ishikawa H., Ma Z., Barber G.N. STING Regulates Intracellular DNA-Mediated, Type I Interferon-Dependent Innate Immunity. Nature. 2009;461:788–792. doi: 10.1038/nature08476. PubMed DOI PMC

Liu S., Cai X., Wu J., Cong Q., Chen X., Li T., Du F., Ren J., Wu Y.-T., Grishin N.V., et al. Phosphorylation of Innate Immune Adaptor Proteins MAVS, STING, and TRIF Induces IRF3 Activation. Science. 2015;347:aaa2630. doi: 10.1126/science.aaa2630. PubMed DOI

Tanaka Y., Chen Z.J. STING Specifies IRF3 Phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway. Sci. Signal. 2012;5:ra20. doi: 10.1126/scisignal.2002521. PubMed DOI PMC

Zhang C., Shang G., Gui X., Zhang X., Bai X., Chen Z.J. Structural Basis of STING Binding with and Phosphorylation by TBK1. Nature. 2019;567:394–398. doi: 10.1038/s41586-019-1000-2. PubMed DOI PMC

Zhong B., Yang Y., Li S., Wang Y.-Y., Li Y., Diao F., Lei C., He X., Zhang L., Tien P., et al. The Adaptor Protein MITA Links Virus-Sensing Receptors to IRF3 Transcription Factor Activation. Immunity. 2008;29:538–550. doi: 10.1016/j.immuni.2008.09.003. PubMed DOI

Parker Z.M., Murphy A.A., Leib D.A. Role of the DNA Sensor STING in Protection from Lethal Infection Following Corneal and Intracerebral Challenge with Herpes Simplex Virus 1. J. Virol. 2015;89:11080–11091. doi: 10.1128/JVI.00954-15. PubMed DOI PMC

Reinert L.S., Lopušná K., Winther H., Sun C., Thomsen M.K., Nandakumar R., Mogensen T.H., Meyer M., Vægter C., Nyengaard J.R., et al. Sensing of HSV-1 by the CGAS–STING Pathway in Microglia Orchestrates Antiviral Defence in the CNS. Nat. Commun. 2016;7:13348. doi: 10.1038/ncomms13348. PubMed DOI PMC

Stetson D.B., Medzhitov R. Recognition of Cytosolic DNA Activates an IRF3-Dependent Innate Immune Response. Immunity. 2006;24:93–103. doi: 10.1016/j.immuni.2005.12.003. PubMed DOI

Stratmann S.A., Morrone S.R., van Oijen A.M., Sohn J. The Innate Immune Sensor IFI16 Recognizes Foreign DNA in the Nucleus by Scanning along the Duplex. eLife. 2015;4:e11721. doi: 10.7554/eLife.11721. PubMed DOI PMC

Ansari M.A., Dutta S., Veettil M.V., Dutta D., Iqbal J., Kumar B., Roy A., Chikoti L., Singh V.V., Chandran B. Herpesvirus Genome Recognition Induced Acetylation of Nuclear IFI16 Is Essential for Its Cytoplasmic Translocation, Inflammasome and IFN-β Responses. PLoS Pathog. 2015;11:e1005019. doi: 10.1371/journal.ppat.1005019. PubMed DOI PMC

Lum K.K., Howard T.R., Pan C., Cristea I.M. Charge-Mediated Pyrin Oligomerization Nucleates Antiviral IFI16 Sensing of Herpesvirus DNA. mBio. 2019;10:e01428-19. doi: 10.1128/mBio.01428-19. PubMed DOI PMC

Orzalli M.H., Broekema N.M., Diner B.A., Hancks D.C., Elde N.C., Cristea I.M., Knipe D.M. CGAS-Mediated Stabilization of IFI16 Promotes Innate Signaling during Herpes Simplex Virus Infection. Proc. Natl. Acad. Sci. USA. 2015;112:E1773–E1781. doi: 10.1073/pnas.1424637112. PubMed DOI PMC

Almine J.F., O’Hare C.A.J., Dunphy G., Haga I.R., Naik R.J., Atrih A., Connolly D.J., Taylor J., Kelsall I.R., Bowie A.G., et al. IFI16 and CGAS Cooperate in the Activation of STING during DNA Sensing in Human Keratinocytes. Nat. Commun. 2017;8:14392. doi: 10.1038/ncomms14392. PubMed DOI PMC

Jønsson K.L., Laustsen A., Krapp C., Skipper K.A., Thavachelvam K., Hotter D., Egedal J.H., Kjolby M., Mohammadi P., Prabakaran T., et al. IFI16 Is Required for DNA Sensing in Human Macrophages by Promoting Production and Function of CGAMP. Nat. Commun. 2017;8:14391. doi: 10.1038/ncomms14391. PubMed DOI PMC

Ishikawa H., Barber G.N. STING Is an Endoplasmic Reticulum Adaptor That Facilitates Innate Immune Signalling. Nature. 2008;455:674–678. doi: 10.1038/nature07317. PubMed DOI PMC

Gentili M., Lahaye X., Nadalin F., Nader G.P.F., Puig Lombardi E., Herve S., De Silva N.S., Rookhuizen D.C., Zueva E., Goudot C., et al. The N-Terminal Domain of CGAS Determines Preferential Association with Centromeric DNA and Innate Immune Activation in the Nucleus. Cell Rep. 2019;26:2377–2393.e13. doi: 10.1016/j.celrep.2019.01.105. PubMed DOI PMC

Barnett K.C., Coronas-Serna J.M., Zhou W., Ernandes M.J., Cao A., Kranzusch P.J., Kagan J.C. Phosphoinositide Interactions Position CGAS at the Plasma Membrane to Ensure Efficient Distinction between Self- and Viral DNA. Cell. 2019;176:1432–1446.e11. doi: 10.1016/j.cell.2019.01.049. PubMed DOI PMC

Li T., Huang T., Du M., Chen X., Du F., Ren J., Chen Z.J. Phosphorylation and Chromatin Tethering Prevent CGAS Activation during Mitosis. Science. 2021;371:eabc5386. doi: 10.1126/science.abc5386. PubMed DOI PMC

Wu X., Wu F.-H., Wang X., Wang L., Siedow J.N., Zhang W., Pei Z.-M. Molecular Evolutionary and Structural Analysis of the Cytosolic DNA Sensor CGAS and STING. Nucleic Acids Res. 2014;42:8243–8257. doi: 10.1093/nar/gku569. PubMed DOI PMC

Xie W., Lama L., Adura C., Tomita D., Glickman J.F., Tuschl T., Patel D.J. Human CGAS Catalytic Domain Has an Additional DNA-Binding Interface That Enhances Enzymatic Activity and Liquid-Phase Condensation. Proc. Natl. Acad. Sci. USA. 2019;116:11946–11955. doi: 10.1073/pnas.1905013116. PubMed DOI PMC

Kranzusch P.J. CGAS and CD-NTase Enzymes: Structure, Mechanism, and Evolution. Curr. Opin. Struct. Biol. 2019;59:178–187. doi: 10.1016/j.sbi.2019.08.003. PubMed DOI PMC

Zhou W., Whiteley A.T., de Oliveira Mann C.C., Morehouse B.R., Nowak R.P., Fischer E.S., Gray N.S., Mekalanos J.J., Kranzusch P.J. Structure of the Human CGAS–DNA Complex Reveals Enhanced Control of Immune Surveillance. Cell. 2018;174:300–311.e11. doi: 10.1016/j.cell.2018.06.026. PubMed DOI PMC

Li X.-D., Wu J., Gao D., Wang H., Sun L., Chen Z.J. Pivotal Roles of CGAS-CGAMP Signaling in Antiviral Defense and Immune Adjuvant Effects. Science. 2013;341:1390–1394. doi: 10.1126/science.1244040. PubMed DOI PMC

Andreeva L., Hiller B., Kostrewa D., Lässig C., de Oliveira Mann C.C., Jan Drexler D., Maiser A., Gaidt M., Leonhardt H., Hornung V., et al. CGAS Senses Long and HMGB/TFAM-Bound U-Turn DNA by Forming Protein–DNA Ladders. Nature. 2017;549:394–398. doi: 10.1038/nature23890. PubMed DOI

Du M., Chen Z.J. DNA-Induced Liquid Phase Condensation of CGAS Activates Innate Immune Signaling. Science. 2018;361:704–709. doi: 10.1126/science.aat1022. PubMed DOI PMC

Liu Z.-S., Cai H., Xue W., Wang M., Xia T., Li W.-J., Xing J.-Q., Zhao M., Huang Y.-J., Chen S., et al. G3BP1 Promotes DNA Binding and Activation of CGAS. Nat. Immunol. 2019;20:18–28. doi: 10.1038/s41590-018-0262-4. PubMed DOI PMC

Srikanth S., Woo J.S., Wu B., El-Sherbiny Y.M., Leung J., Chupradit K., Rice L., Seo G.J., Calmettes G., Ramakrishna C., et al. The Ca2+ Sensor STIM1 Regulates the Type I Interferon Response by Retaining the Signaling Adaptor STING at the Endoplasmic Reticulum. Nat. Immunol. 2019;20:152–162. doi: 10.1038/s41590-018-0287-8. PubMed DOI PMC

Burdette D.L., Monroe K.M., Sotelo-Troha K., Iwig J.S., Eckert B., Hyodo M., Hayakawa Y., Vance R.E. STING Is a Direct Innate Immune Sensor of Cyclic Di-GMP. Nature. 2011;478:515–518. doi: 10.1038/nature10429. PubMed DOI PMC

Diner E.J., Burdette D.L., Wilson S.C., Monroe K.M., Kellenberger C.A., Hyodo M., Hayakawa Y., Hammond M.C., Vance R.E. The Innate Immune DNA Sensor CGAS Produces a Noncanonical Cyclic Dinucleotide That Activates Human STING. Cell Rep. 2013;3:1355–1361. doi: 10.1016/j.celrep.2013.05.009. PubMed DOI PMC

Cheng Z., Dai T., He X., Zhang Z., Xie F., Wang S., Zhang L., Zhou F. The Interactions between CGAS-STING Pathway and Pathogens. Sig. Transduct. Target. Ther. 2020;5:91. doi: 10.1038/s41392-020-0198-7. PubMed DOI PMC

Shang G., Zhang C., Chen Z.J., Bai X., Zhang X. Cryo-EM Structures of STING Reveal Its Mechanism of Activation by Cyclic GMP–AMP. Nature. 2019;567:389–393. doi: 10.1038/s41586-019-0998-5. PubMed DOI PMC

Gui X., Yang H., Li T., Tan X., Shi P., Li M., Du F., Chen Z.J. Autophagy Induction via STING Trafficking Is a Primordial Function of the CGAS Pathway. Nature. 2019;567:262–266. doi: 10.1038/s41586-019-1006-9. PubMed DOI PMC

Stempel M., Chan B., Juranić Lisnić V., Krmpotić A., Hartung J., Paludan S.R., Füllbrunn N., Lemmermann N.A., Brinkmann M.M. The Herpesviral Antagonist M152 Reveals Differential Activation of STING -dependent IRF and NF -κB Signaling and STING ’s Dual Role during MCMV Infection. EMBO J. 2019;38:e100983. doi: 10.15252/embj.2018100983. PubMed DOI PMC

Tsuchida T., Zou J., Saitoh T., Kumar H., Abe T., Matsuura Y., Kawai T., Akira S. The Ubiquitin Ligase TRIM56 Regulates Innate Immune Responses to Intracellular Double-Stranded DNA. Immunity. 2010;33:765–776. doi: 10.1016/j.immuni.2010.10.013. PubMed DOI

Wang Q., Liu X., Cui Y., Tang Y., Chen W., Li S., Yu H., Pan Y., Wang C. The E3 Ubiquitin Ligase AMFR and INSIG1 Bridge the Activation of TBK1 Kinase by Modifying the Adaptor STING. Immunity. 2014;41:919–933. doi: 10.1016/j.immuni.2014.11.011. PubMed DOI

Zhang J., Hu M.-M., Wang Y.-Y., Shu H.-B. TRIM32 Protein Modulates Type I Interferon Induction and Cellular Antiviral Response by Targeting MITA/STING Protein for K63-Linked Ubiquitination. J. Biol. Chem. 2012;287:28646–28655. doi: 10.1074/jbc.M112.362608. PubMed DOI PMC

Yu X., Zhang L., Shen J., Zhai Y., Jiang Q., Yi M., Deng X., Ruan Z., Fang R., Chen Z., et al. The STING Phase-Separator Suppresses Innate Immune Signalling. Nat. Cell Biol. 2021;23:330–340. doi: 10.1038/s41556-021-00659-0. PubMed DOI

Agelidis A.M., Shukla D. Cell Entry Mechanisms of HSV: What We Have Learned in Recent Years. Future Virol. 2015;10:1145–1154. doi: 10.2217/fvl.15.85. PubMed DOI PMC

Oh J., Fraser N.W. Temporal Association of the Herpes Simplex Virus Genome with Histone Proteins during a Lytic Infection. J. Virol. 2008;82:3530–3537. doi: 10.1128/JVI.00586-07. PubMed DOI PMC

Thorley-Lawson D.A., Duca K.A., Shapiro M. Epstein-Barr Virus: A Paradigm for Persistent Infection—For Real and in Virtual Reality. Trends Immunol. 2008;29:195–201. doi: 10.1016/j.it.2008.01.006. PubMed DOI

Weidner-Glunde M., Kruminis-Kaszkiel E., Savanagouder M. Herpesviral Latency—Common Themes. Pathogens. 2020;9:125. doi: 10.3390/pathogens9020125. PubMed DOI PMC

Varani S., Cederarv M., Feld S., Tammik C., Frascaroli G., Landini M.P., Söderberg-Nauclér C. Human Cytomegalovirus Differentially Controls B Cell and T Cell Responses through Effects on Plasmacytoid Dendritic Cells. J. Immunol. 2007;179:7767–7776. doi: 10.4049/jimmunol.179.11.7767. PubMed DOI

Krug A., Luker G.D., Barchet W., Leib D.A., Akira S., Colonna M. Herpes Simplex Virus Type 1 Activates Murine Natural Interferon-Producing Cells through Toll-like Receptor 9. Blood. 2004;103:1433–1437. doi: 10.1182/blood-2003-08-2674. PubMed DOI

Zyzak J., Mitkiewicz M., Leszczyńska E., Reniewicz P., Moynagh P.N., Siednienko J. HSV-1/TLR9-Mediated IFNβ and TNFα Induction Is Mal-Dependent in Macrophages. J. Innate Immun. 2020;12:387–398. doi: 10.1159/000504542. PubMed DOI PMC

Hochrein H., Schlatter B., O’Keeffe M., Wagner C., Schmitz F., Schiemann M., Bauer S., Suter M., Wagner H. Herpes Simplex Virus Type-1 Induces IFN- Production via Toll-like Receptor 9-Dependent and -Independent Pathways. Proc. Natl. Acad. Sci. USA. 2004;101:11416–11421. doi: 10.1073/pnas.0403555101. PubMed DOI PMC

Lund J., Sato A., Akira S., Medzhitov R., Iwasaki A. Toll-like Receptor 9–Mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells. J. Exp. Med. 2003;198:513–520. doi: 10.1084/jem.20030162. PubMed DOI PMC

Orzalli M.H., DeLuca N.A., Knipe D.M. Nuclear IFI16 Induction of IRF-3 Signaling during Herpesviral Infection and Degradation of IFI16 by the Viral ICP0 Protein. Proc. Natl. Acad. Sci. USA. 2012;109:E3008–E3017. doi: 10.1073/pnas.1211302109. PubMed DOI PMC

Duan Y., Zeng J., Fan S., Liao Y., Feng M., Wang L., Zhang Y., Li Q. Herpes Simplex Virus Type 1-Encoded MiR-H2-3p Manipulates Cytosolic DNA-Stimulated Antiviral Innate Immune Response by Targeting DDX41. Viruses. 2019;11:756. doi: 10.3390/v11080756. PubMed DOI PMC

Justice J.L., Kennedy M.A., Hutton J.E., Liu D., Song B., Phelan B., Cristea I.M. Systematic Profiling of Protein Complex Dynamics Reveals DNA-PK Phosphorylation of IFI16 En Route to Herpesvirus Immunity. Sci. Adv. 2021;7:eabg6680. doi: 10.1126/sciadv.abg6680. PubMed DOI PMC

Yamashiro L.H., Wilson S.C., Morrison H.M., Karalis V., Chung J.-Y.J., Chen K.J., Bateup H.S., Szpara M.L., Lee A.Y., Cox J.S., et al. Interferon-Independent STING Signaling Promotes Resistance to HSV-1 in Vivo. Nat. Commun. 2020;11:3382. doi: 10.1038/s41467-020-17156-x. PubMed DOI PMC

Wu J., Dobbs N., Yang K., Yan N. Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion. Immunity. 2020;53:115–126.e5. doi: 10.1016/j.immuni.2020.06.009. PubMed DOI PMC

Kerur N., Veettil M.V., Sharma-Walia N., Bottero V., Sadagopan S., Otageri P., Chandran B. IFI16 Acts as a Nuclear Pathogen Sensor to Induce the Inflammasome in Response to Kaposi Sarcoma-Associated Herpesvirus Infection. Cell Host Microbe. 2011;9:363–375. doi: 10.1016/j.chom.2011.04.008. PubMed DOI PMC

Johnson K.E., Chikoti L., Chandran B. Herpes Simplex Virus 1 Infection Induces Activation and Subsequent Inhibition of the IFI16 and NLRP3 Inflammasomes. J. Virol. 2013;87:5005–5018. doi: 10.1128/JVI.00082-13. PubMed DOI PMC

Ansari M.A., Singh V.V., Dutta S., Veettil M.V., Dutta D., Chikoti L., Lu J., Everly D., Chandran B. Constitutive Interferon-Inducible Protein 16-Inflammasome Activation during Epstein-Barr Virus Latency I, II, and III in B and Epithelial Cells. J. Virol. 2013;87:8606–8623. doi: 10.1128/JVI.00805-13. PubMed DOI PMC

Iqbal J., Ansari M.A., Kumar B., Dutta D., Roy A., Chikoti L., Pisano G., Dutta S., Vahedi S., Veettil M.V., et al. Histone H2B-IFI16 Recognition of Nuclear Herpesviral Genome Induces Cytoplasmic Interferon-β Responses. PLoS Pathog. 2016;12:e1005967. doi: 10.1371/journal.ppat.1005967. PubMed DOI PMC

Dutta D., Dutta S., Veettil M.V., Roy A., Ansari M.A., Iqbal J., Chikoti L., Kumar B., Johnson K.E., Chandran B. BRCA1 Regulates IFI16 Mediated Nuclear Innate Sensing of Herpes Viral DNA and Subsequent Induction of the Innate Inflammasome and Interferon-β Responses. PLoS Pathog. 2015;11:e1005030. doi: 10.1371/journal.ppat.1005030. PubMed DOI PMC

Su C., Zheng C. Herpes Simplex Virus 1 Abrogates the CGAS/STING-Mediated Cytosolic DNA-Sensing Pathway via Its Virion Host Shutoff Protein, UL41. J. Virol. 2017;91:e02414-16. doi: 10.1128/JVI.02414-16. PubMed DOI PMC

Huang J., You H., Su C., Li Y., Chen S., Zheng C. Herpes Simplex Virus 1 Tegument Protein VP22 Abrogates CGAS/STING-Mediated Antiviral Innate Immunity. J. Virol. 2018;92:e00841-18. doi: 10.1128/JVI.00841-18. PubMed DOI PMC

Teigler J.E., Kagan J.C., Barouch D.H. Late Endosomal Trafficking of Alternative Serotype Adenovirus Vaccine Vectors Augments Antiviral Innate Immunity. J. Virol. 2014;88:10354–10363. doi: 10.1128/JVI.00936-14. PubMed DOI PMC

Basner-Tschakarjan E., Gaffal E., O’Keeffe M., Tormo D., Limmer A., Wagner H., Hochrein H., Tüting T. Adenovirus Efficiently Transduces Plasmacytoid Dendritic Cells Resulting in TLR9-Dependent Maturation and IFN-α Production. J. Gene Med. 2006;8:1300–1306. doi: 10.1002/jgm.964. PubMed DOI

Hensley S.E., Giles-Davis W., McCoy K.C., Weninger W., Ertl H.C.J. Dendritic Cell Maturation, but Not CD8 + T Cell Induction, Is Dependent on Type I IFN Signaling during Vaccination with Adenovirus Vectors. J. Immunol. 2005;175:6032–6041. doi: 10.4049/jimmunol.175.9.6032. PubMed DOI

Huarte E., Larrea E., Hernández-Alcoceba R., Alfaro C., Murillo O., Arina A., Tirapu I., Azpilicueta A., Hervás-Stubbs S., Bortolanza S., et al. Recombinant Adenoviral Vectors Turn on the Type I Interferon System without Inhibition of Transgene Expression and Viral Replication. Mol. Ther. 2006;14:129–138. doi: 10.1016/j.ymthe.2006.02.015. PubMed DOI

Zhu J., Huang X., Yang Y. Innate Immune Response to Adenoviral Vectors Is Mediated by Both Toll-Like Receptor-Dependent and -Independent Pathways. J. Virol. 2007;81:3170–3180. doi: 10.1128/JVI.02192-06. PubMed DOI PMC

Iacobelli-Martinez M., Nemerow G.R. Preferential Activation of Toll-Like Receptor Nine by CD46-Utilizing Adenoviruses. J. Virol. 2007;81:1305–1312. doi: 10.1128/JVI.01926-06. PubMed DOI PMC

McGuire K.A., Barlan A.U., Griffin T.M., Wiethoff C.M. Adenovirus Type 5 Rupture of Lysosomes Leads to Cathepsin B-Dependent Mitochondrial Stress and Production of Reactive Oxygen Species. J. Virol. 2011;85:10806–10813. doi: 10.1128/JVI.00675-11. PubMed DOI PMC

Barlan A.U., Griffin T.M., Mcguire K.A., Wiethoff C.M. Adenovirus Membrane Penetration Activates the NLRP3 Inflammasome. J. Virol. 2011;85:146–155. doi: 10.1128/JVI.01265-10. PubMed DOI PMC

Lam E., Stein S., Falck-Pedersen E. Adenovirus Detection by the CGAS/STING/TBK1 DNA Sensing Cascade. J. Virol. 2014;88:974–981. doi: 10.1128/JVI.02702-13. PubMed DOI PMC

Stein S.C., Falck-Pedersen E. Sensing Adenovirus Infection: Activation of Interferon Regulatory Factor 3 in RAW 264.7 Cells. J. Virol. 2012;86:4527–4537. doi: 10.1128/JVI.07071-11. PubMed DOI PMC

Yamaguchi T., Kawabata K., Kouyama E., Ishii K.J., Katayama K., Suzuki T., Kurachi S., Sakurai F., Akira S., Mizuguchi H. Induction of Type I Interferon by Adenovirus-Encoded Small RNAs. Proc. Natl. Acad. Sci. USA. 2010;107:17286–17291. doi: 10.1073/pnas.1009823107. PubMed DOI PMC

Sohn S.-Y., Hearing P. Mechanism of Adenovirus E4-ORF3-Mediated SUMO Modifications. mBio. 2019;10:e00022-19. doi: 10.1128/mBio.00022-19. PubMed DOI PMC

Lau L., Gray E.E., Brunette R.L., Stetson D.B. DNA Tumor Virus Oncogenes Antagonize the CGAS-STING DNA-Sensing Pathway. Science. 2015;350:568–571. doi: 10.1126/science.aab3291. PubMed DOI

Look D.C., Roswit W.T., Frick A.G., Gris-Alevy Y., Dickhaus D.M., Walter M.J., Holtzman M.J. Direct Suppression of Stat1 Function during Adenoviral Infection. Immunity. 1998;9:871–880. doi: 10.1016/S1074-7613(00)80652-4. PubMed DOI

McBride A.A. Human Papillomaviruses: Diversity, Infection and Host Interactions. Nat. Rev. Microbiol. 2022;20:95–108. doi: 10.1038/s41579-021-00617-5. PubMed DOI

Doorbar J., Quint W., Banks L., Bravo I.G., Stoler M., Broker T.R., Stanley M.A. The Biology and Life-Cycle of Human Papillomaviruses. Vaccine. 2012;30:F55–F70. doi: 10.1016/j.vaccine.2012.06.083. PubMed DOI

Day P.M., Thompson C.D., Schowalter R.M., Lowy D.R., Schiller J.T. Identification of a Role for the Trans-Golgi Network in Human Papillomavirus 16 Pseudovirus Infection. J. Virol. 2013;87:3862–3870. doi: 10.1128/JVI.03222-12. PubMed DOI PMC

Aydin I., Weber S., Snijder B., Samperio Ventayol P., Kühbacher A., Becker M., Day P.M., Schiller J.T., Kann M., Pelkmans L., et al. Large Scale RNAi Reveals the Requirement of Nuclear Envelope Breakdown for Nuclear Import of Human Papillomaviruses. PLoS Pathog. 2014;10:e1004162. doi: 10.1371/journal.ppat.1004162. PubMed DOI PMC

Cannella F., Pierangeli A., Scagnolari C., Cacciotti G., Tranquilli G., Stentella P., Recine N., Antonelli G. TLR9 Is Expressed in Human Papillomavirus-Positive Cervical Cells and Is Overexpressed in Persistent Infections. Immunobiology. 2015;220:363–368. doi: 10.1016/j.imbio.2014.10.012. PubMed DOI

Hasan U.A., Bates E., Takeshita F., Biliato A., Accardi R., Bouvard V., Mansour M., Vincent I., Gissmann L., Iftner T., et al. TLR9 Expression and Function Is Abolished by the Cervical Cancer-Associated Human Papillomavirus Type 16. J. Immunol. 2007;178:3186–3197. doi: 10.4049/jimmunol.178.5.3186. PubMed DOI

Reinholz M., Kawakami Y., Salzer S., Kreuter A., Dombrowski Y., Koglin S., Kresse S., Ruzicka T., Schauber J. HPV16 Activates the AIM2 Inflammasome in Keratinocytes. Arch. Dermatol. Res. 2013;305:723–732. doi: 10.1007/s00403-013-1375-0. PubMed DOI

Ainouze M., Rochefort P., Parroche P., Roblot G., Tout I., Briat F., Zannetti C., Marotel M., Goutagny N., Auron P., et al. Human Papillomavirus Type 16 Antagonizes IRF6 Regulation of IL-1β. PLoS Pathog. 2018;14:e1007158. doi: 10.1371/journal.ppat.1007158. PubMed DOI PMC

Uhlorn B.L., Jackson R., Li S., Bratton S.M., Van Doorslaer K., Campos S.K. Vesicular Trafficking Permits Evasion of CGAS/STING Surveillance during Initial Human Papillomavirus Infection. PLoS Pathog. 2020;16:e1009028. doi: 10.1371/journal.ppat.1009028. PubMed DOI PMC

Shaikh M.H., Bortnik V., McMillan N.A.J., Idris A. CGAS-STING Responses Are Dampened in High-Risk HPV Type 16 Positive Head and Neck Squamous Cell Carcinoma Cells. Microb. Pathog. 2019;132:162–165. doi: 10.1016/j.micpath.2019.05.004. PubMed DOI

Cook L. Polyomaviruses. Microbiol. Spectr. 2016;4 doi: 10.1128/microbiolspec.DMIH2-0010-2015. PubMed DOI

Prado J., Monezi T., Amorim A., Lino V., Paladino A., Boccardo E. Human Polyomaviruses and Cancer: An Overview. Clinics. 2018;73 doi: 10.6061/clinics/2018/e558s. PubMed DOI PMC

Ehlers B., Moens U. Genome Analysis of Non-Human Primate Polyomaviruses. Infect. Genet. Evol. 2014;26:283–294. doi: 10.1016/j.meegid.2014.05.030. PubMed DOI

Soldatova I., Prilepskaja T., Abrahamyan L., Forstová J., Huérfano S. Interaction of the Mouse Polyomavirus Capsid Proteins with Importins Is Required for Efficient Import of Viral DNA into the Cell Nucleus. Viruses. 2018;10:165. doi: 10.3390/v10040165. PubMed DOI PMC

Liebl D., Difato F., Horníková L., Mannová P., Štokrová J., Forstová J. Mouse Polyomavirus Enters Early Endosomes, Requires Their Acidic PH for Productive Infection, and Meets Transferrin Cargo in Rab11-Positive Endosomes. J. Virol. 2006;80:4610–4622. doi: 10.1128/JVI.80.9.4610-4622.2006. PubMed DOI PMC

Horníková L., Bruštíková K., Forstová J. Microtubules in Polyomavirus Infection. Viruses. 2020;12:121. doi: 10.3390/v12010121. PubMed DOI PMC

Huérfano S., Ryabchenko B., Španielová H., Forstová J. Hydrophobic Domains of Mouse Polyomavirus Minor Capsid Proteins Promote Membrane Association and Virus Exit from the ER. FEBS J. 2017;284:883–902. doi: 10.1111/febs.14033. PubMed DOI

Padgett B.L., Zurhein G.M., Walker D.L., Eckroade R., Dessel B. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet. 1971;297:1257–1260. doi: 10.1016/S0140-6736(71)91777-6. PubMed DOI

Gardner S.D., Field A.M., Coleman D.V., Hulme B. New human papovavirus (B.K.) Isolated from urine after renal transplantation. Lancet. 1971;297:1253–1257. doi: 10.1016/S0140-6736(71)91776-4. PubMed DOI

Feng H., Shuda M., Chang Y., Moore P.S. Clonal Integration of a Polyomavirus in Human Merkel Cell Carcinoma. Science. 2008;319:1096–1100. doi: 10.1126/science.1152586. PubMed DOI PMC

Knowles W.A., Pipkin P., Andrews N., Vyse A., Minor P., Brown D.W.G., Miller E. Population-Based Study of Antibody to the Human Polyomaviruses BKV and JCV and the Simian Polyomavirus SV40. J. Med. Virol. 2003;71:115–123. doi: 10.1002/jmv.10450. PubMed DOI

Egli A., Infanti L., Dumoulin A., Buser A., Samaridis J., Stebler C., Gosert R., Hirsch H.H. Prevalence of Polyomavirus BK and JC Infection and Replication in 400 Healthy Blood Donors. J. Infect. Dis. 2009;199:837–846. doi: 10.1086/597126. PubMed DOI

Šroller V., Hamšíková E., Ludvíková V., Vochozková P., Kojzarová M., Fraiberk M., Saláková M., Morávková A., Forstová J., Němečková Š. Seroprevalence Rates of BKV, JCV, and MCPyV Polyomaviruses in the General Czech Republic Population: Seroprevalence of BKV, JCV, and MCPyV. J. Med. Virol. 2014;86:1560–1568. doi: 10.1002/jmv.23841. PubMed DOI

Foulongne V., Sauvage V., Hebert C., Dereure O., Cheval J., Gouilh M.A., Pariente K., Segondy M., Burguière A., Manuguerra J.-C., et al. Human Skin Microbiota: High Diversity of DNA Viruses Identified on the Human Skin by High Throughput Sequencing. PLoS ONE. 2012;7:e38499. doi: 10.1371/journal.pone.0038499. PubMed DOI PMC

Jouhi L., Koljonen V., Böhling T., Haglund C., Hagström J. The Expression of Toll-like Receptors 2, 4, 5, 7 and 9 in Merkel Cell Carcinoma. Anticancer. Res. 2015;35:1843–1849. PubMed

Shahzad N., Shuda M., Gheit T., Kwun H.J., Cornet I., Saidj D., Zannetti C., Hasan U., Chang Y., Moore P.S., et al. The T Antigen Locus of Merkel Cell Polyomavirus Downregulates Human Toll-Like Receptor 9 Expression. J. Virol. 2013;87:13009–13019. doi: 10.1128/JVI.01786-13. PubMed DOI PMC

Ryabchenko B., Soldatova I., Šroller V., Forstová J., Huérfano S. Immune Sensing of Mouse Polyomavirus DNA by P204 and CGAS DNA Sensors. FEBS J. 2021;288:5964–5985. doi: 10.1111/febs.15962. PubMed DOI PMC

Krump N.A., Wang R., Liu W., Yang J.F., Ma T., You J. Merkel Cell Polyomavirus Infection Induces an Antiviral Innate Immune Response in Human Dermal Fibroblasts. J. Virol. 2021;95:e02211-20. doi: 10.1128/JVI.02211-20. PubMed DOI PMC

Liu W., Yang R., Payne A.S., Schowalter R.M., Spurgeon M.E., Lambert P.F., Xu X., Buck C.B., You J. Identifying the Target Cells and Mechanisms of Merkel Cell Polyomavirus Infection. Cell Host Microbe. 2016;19:775–787. doi: 10.1016/j.chom.2016.04.024. PubMed DOI PMC

Mannová P., Forstová J. Mouse Polyomavirus Utilizes Recycling Endosomes for a Traffic Pathway Independent of COPI Vesicle Transport. J. Virol. 2003;77:1672–1681. doi: 10.1128/JVI.77.3.1672-1681.2003. PubMed DOI PMC

de Kort H., Heutinck K.M., Ruben J.M., Ede V. Silva A., Wolthers K.C., Hamann J., ten Berge I.J.M. Primary Human Renal-Derived Tubular Epithelial Cells Fail to Recognize and Suppress BK Virus Infection. Transplantation. 2017;101:1820–1829. doi: 10.1097/TP.0000000000001521. PubMed DOI

An P., Sáenz Robles M.T., Duray A.M., Cantalupo P.G., Pipas J.M. Human Polyomavirus BKV Infection of Endothelial Cells Results in Interferon Pathway Induction and Persistence. PLoS Pathog. 2019;15:e1007505. doi: 10.1371/journal.ppat.1007505. PubMed DOI PMC

Manzetti J., Weissbach F.H., Graf F.E., Unterstab G., Wernli M., Hopfer H., Drachenberg C.B., Rinaldo C.H., Hirsch H.H. BK Polyomavirus Evades Innate Immune Sensing by Disrupting the Mitochondrial Network and Promotes Mitophagy. iScience. 2020;23:101257. doi: 10.1016/j.isci.2020.101257. PubMed DOI PMC

Yan H., Zhong G., Xu G., He W., Jing Z., Gao Z., Huang Y., Qi Y., Peng B., Wang H., et al. Sodium Taurocholate Cotransporting Polypeptide Is a Functional Receptor for Human Hepatitis B and D Virus. eLife. 2012;1:e00049. doi: 10.7554/eLife.00049. PubMed DOI PMC

Huang H.-C., Chen C.-C., Chang W.-C., Tao M.-H., Huang C. Entry of Hepatitis B Virus into Immortalized Human Primary Hepatocytes by Clathrin-Dependent Endocytosis. J. Virol. 2012;86:9443–9453. doi: 10.1128/JVI.00873-12. PubMed DOI PMC

Macovei A., Radulescu C., Lazar C., Petrescu S., Durantel D., Dwek R.A., Zitzmann N., Nichita N.B. Hepatitis B Virus Requires Intact Caveolin-1 Function for Productive Infection in HepaRG Cells. J. Virol. 2010;84:243–253. doi: 10.1128/JVI.01207-09. PubMed DOI PMC

Bock C.T., Schwinn S., Locarnini S., Fyfe J., Manns M.P., Trautwein C., Zentgraf H. Structural Organization of the Hepatitis B Virus Minichromosome. J. Mol. Biol. 2001;307:183–196. doi: 10.1006/jmbi.2000.4481. PubMed DOI

Mutz P., Metz P., Lempp F.A., Bender S., Qu B., Schöneweis K., Seitz S., Tu T., Restuccia A., Frankish J., et al. HBV Bypasses the Innate Immune Response and Does Not Protect HCV From Antiviral Activity of Interferon. Gastroenterology. 2018;154:1791–1804.e22. doi: 10.1053/j.gastro.2018.01.044. PubMed DOI

Suslov A., Boldanova T., Wang X., Wieland S., Heim M.H. Hepatitis B Virus Does Not Interfere With Innate Immune Responses in the Human Liver. Gastroenterology. 2018;154:1778–1790. doi: 10.1053/j.gastro.2018.01.034. PubMed DOI

Chen Y., Tian Z. HBV-Induced Immune Imbalance in the Development of HCC. Front. Immunol. 2019;10:2048. doi: 10.3389/fimmu.2019.02048. PubMed DOI PMC

Hirsch I., Caux C., Hasan U., Bendriss-Vermare N., Olive D. Impaired Toll-like Receptor 7 and 9 Signaling: From Chronic Viral Infections to Cancer. Trends Immunol. 2010;31:391–397. doi: 10.1016/j.it.2010.07.004. PubMed DOI

Vincent I.E., Zannetti C., Lucifora J., Norder H., Protzer U., Hainaut P., Zoulim F., Tommasino M., Trépo C., Hasan U., et al. Hepatitis B Virus Impairs TLR9 Expression and Function in Plasmacytoid Dendritic Cells. PLoS ONE. 2011;6:e26315. doi: 10.1371/journal.pone.0026315. PubMed DOI PMC

Xu Y., Hu Y., Shi B., Zhang X., Wang J., Zhang Z., Shen F., Zhang Q., Sun S., Yuan Z. HBsAg Inhibits TLR9-Mediated Activation and IFN-α Production in Plasmacytoid Dendritic Cells. Mol. Immunol. 2009;46:2640–2646. doi: 10.1016/j.molimm.2009.04.031. PubMed DOI

Wu J., Lu M., Meng Z., Trippler M., Broering R., Szczeponek A., Krux F., Dittmer U., Roggendorf M., Gerken G., et al. Toll-like Receptor-Mediated Control of HBV Replication by Nonparenchymal Liver Cells in Mice. Hepatology. 2007;46:1769–1778. doi: 10.1002/hep.21897. PubMed DOI

Martinet J., Dufeu–Duchesne T., Bruder Costa J., Larrat S., Marlu A., Leroy V., Plumas J., Aspord C. Altered Functions of Plasmacytoid Dendritic Cells and Reduced Cytolytic Activity of Natural Killer Cells in Patients With Chronic HBV Infection. Gastroenterology. 2012;143:1586–1596.e8. doi: 10.1053/j.gastro.2012.08.046. PubMed DOI

Verrier E.R., Yim S., Heydmann L., El Saghire H., Bach C., Turon-Lagot V., Mailly L., Durand S.C., Lucifora J., Durantel D., et al. Hepatitis B Virus Evasion From Cyclic Guanosine Monophosphate–Adenosine Monophosphate Synthase Sensing in Human Hepatocytes. Hepatology. 2018;68:1695–1709. doi: 10.1002/hep.30054. PubMed DOI PMC

Chen H., He G., Chen Y., Zhang X. Hepatitis B Virus Might Be Sensed by STING-Dependent DNA Sensors and Attenuates the Response of STING-Dependent DNA Sensing Pathway in Humans with Acute and Chronic Hepatitis B Virus Infection. Viral Immunol. 2020;33:642–651. doi: 10.1089/vim.2020.0096. PubMed DOI

Thomsen M.K., Nandakumar R., Stadler D., Malo A., Valls R.M., Wang F., Reinert L.S., Dagnaes-Hansen F., Hollensen A.K., Mikkelsen J.G., et al. Lack of Immunological DNA Sensing in Hepatocytes Facilitates Hepatitis B Virus Infection. Hepatology. 2016;64:746–759. doi: 10.1002/hep.28685. PubMed DOI

Lauterbach-Rivière L., Bergez M., Mönch S., Qu B., Riess M., Vondran F.W.R., Liese J., Hornung V., Urban S., König R. Hepatitis B Virus DNA Is a Substrate for the CGAS/STING Pathway but Is Not Sensed in Infected Hepatocytes. Viruses. 2020;12:592. doi: 10.3390/v12060592. PubMed DOI PMC

Liu Y., Li J., Chen J., Li Y., Wang W., Du X., Song W., Zhang W., Lin L., Yuan Z. Hepatitis B Virus Polymerase Disrupts K63-Linked Ubiquitination of STING To Block Innate Cytosolic DNA-Sensing Pathways. J. Virol. 2015;89:2287–2300. doi: 10.1128/JVI.02760-14. PubMed DOI PMC

Hu J., Tang L., Cheng J., Zhou T., Li Y., Chang J., Zhao Q., Guo J.-T. Hepatitis B Virus Nucleocapsid Uncoating: Biological Consequences and Regulation by Cellular Nucleases. Emerg. Microbes Infect. 2021;10:852–864. doi: 10.1080/22221751.2021.1919034. PubMed DOI PMC

Chen H., He G., Chen Y., Zhang X., Wu S. Differential Activation of NLRP3, AIM2, and IFI16 Inflammasomes in Humans with Acute and Chronic Hepatitis B. Viral Immunol. 2018;31:639–645. doi: 10.1089/vim.2018.0058. PubMed DOI

Lu Y.-Q., Wu J., Wu X.-J., Ma H., Ma Y.-X., Zhang R., Su M.-N., Wu N., Chen G.-Y., Chen H.-S., et al. Interferon Gamma-Inducible Protein 16 of Peripheral Blood Mononuclear Cells May Sense Hepatitis B Virus Infection and Regulate the Antiviral Immunity. Front. Cell. Infect. Microbiol. 2021;11:790036. doi: 10.3389/fcimb.2021.790036. PubMed DOI PMC

Yang Y., Zhao X., Wang Z., Shu W., Li L., Li Y., Guo Z., Gao B., Xiong S. Nuclear Sensor Interferon-Inducible Protein 16 Inhibits the Function of Hepatitis B Virus Covalently Closed Circular DNA by Integrating Innate Immune Activation and Epigenetic Suppression. Hepatology. 2020;71:1154–1169. doi: 10.1002/hep.30897. PubMed DOI

Wilen C.B., Tilton J.C., Doms R.W. HIV: Cell Binding and Entry. Cold Spring Harb. Perspect. Med. 2012;2:a006866. doi: 10.1101/cshperspect.a006866. PubMed DOI PMC

Zila V., Margiotta E., Turoňová B., Müller T.G., Zimmerli C.E., Mattei S., Allegretti M., Börner K., Rada J., Müller B., et al. Cone-Shaped HIV-1 Capsids Are Transported through Intact Nuclear Pores. Cell. 2021;184:1032–1046.e18. doi: 10.1016/j.cell.2021.01.025. PubMed DOI PMC

Shen Q., Wu C., Freniere C., Tripler T.N., Xiong Y. Nuclear Import of HIV-1. Viruses. 2021;13:2242. doi: 10.3390/v13112242. PubMed DOI PMC

Hatziioannou T., Perez-Caballero D., Cowan S., Bieniasz P.D. Cyclophilin Interactions with Incoming Human Immunodeficiency Virus Type 1 Capsids with Opposing Effects on Infectivity in Human Cells. J. Virol. 2005;79:176–183. doi: 10.1128/JVI.79.1.176-183.2005. PubMed DOI PMC

Nyamweya S., Hegedus A., Jaye A., Rowland-Jones S., Flanagan K.L., Macallan D.C. Comparing HIV-1 and HIV-2 Infection: Lessons for Viral Immunopathogenesis: Comparisons between HIV-1 and HIV-2 Infection. Rev. Med. Virol. 2013;23:221–240. doi: 10.1002/rmv.1739. PubMed DOI

Lahaye X., Manel N. Viral and Cellular Mechanisms of the Innate Immune Sensing of HIV. Curr. Opin. Virol. 2015;11:55–62. doi: 10.1016/j.coviro.2015.01.013. PubMed DOI

Gottlieb G.S., Raugi D.N., Smith R.A. 90-90-90 for HIV-2? Ending the HIV-2 Epidemic by Enhancing Care and Clinical Management of Patients Infected with HIV-2. Lancet HIV. 2018;5:e390–e399. doi: 10.1016/S2352-3018(18)30094-8. PubMed DOI

Gao D., Wu J., Wu Y.-T., Du F., Aroh C., Yan N., Sun L., Chen Z.J. Cyclic GMP-AMP Synthase Is an Innate Immune Sensor of HIV and Other Retroviruses. Science. 2013;341:903–906. doi: 10.1126/science.1240933. PubMed DOI PMC

Jakobsen M.R., Bak R.O., Andersen A., Berg R.K., Jensen S.B., Jin T., Laustsen A., Hansen K., Ostergaard L., Fitzgerald K.A., et al. PNAS Plus: From the Cover: IFI16 Senses DNA Forms of the Lentiviral Replication Cycle and Controls HIV-1 Replication. Proc. Natl. Acad. Sci. USA. 2013;110:E4571–E4580. doi: 10.1073/pnas.1311669110. PubMed DOI PMC

Goldstone D.C., Ennis-Adeniran V., Hedden J.J., Groom H.C.T., Rice G.I., Christodoulou E., Walker P.A., Kelly G., Haire L.F., Yap M.W., et al. HIV-1 Restriction Factor SAMHD1 Is a Deoxynucleoside Triphosphate Triphosphohydrolase. Nature. 2011;480:379–382. doi: 10.1038/nature10623. PubMed DOI

Goujon C., Rivière L., Jarrosson-Wuilleme L., Bernaud J., Rigal D., Darlix J.-L., Cimarelli A. SIVSM/HIV-2 Vpx Proteins Promote Retroviral Escape from a Proteasome-Dependent Restriction Pathway Present in Human Dendritic Cells. Retrovirology. 2007;4:2. doi: 10.1186/1742-4690-4-2. PubMed DOI PMC

Hrecka K., Hao C., Gierszewska M., Swanson S.K., Kesik-Brodacka M., Srivastava S., Florens L., Washburn M.P., Skowronski J. Vpx Relieves Inhibition of HIV-1 Infection of Macrophages Mediated by the SAMHD1 Protein. Nature. 2011;474:658–661. doi: 10.1038/nature10195. PubMed DOI PMC

Laguette N., Sobhian B., Casartelli N., Ringeard M., Chable-Bessia C., Ségéral E., Yatim A., Emiliani S., Schwartz O., Benkirane M. SAMHD1 Is the Dendritic- and Myeloid-Cell-Specific HIV-1 Restriction Factor Counteracted by Vpx. Nature. 2011;474:654–657. doi: 10.1038/nature10117. PubMed DOI PMC

Lahaye X., Satoh T., Gentili M., Cerboni S., Conrad C., Hurbain I., El Marjou A., Lacabaratz C., Lelièvre J.-D., Manel N. The Capsids of HIV-1 and HIV-2 Determine Immune Detection of the Viral CDNA by the Innate Sensor CGAS in Dendritic Cells. Immunity. 2013;39:1132–1142. doi: 10.1016/j.immuni.2013.11.002. PubMed DOI

Lahaye X., Gentili M., Silvin A., Conrad C., Picard L., Jouve M., Zueva E., Maurin M., Nadalin F., Knott G.J., et al. NONO Detects the Nuclear HIV Capsid to Promote CGAS-Mediated Innate Immune Activation. Cell. 2018;175:488–501.e22. doi: 10.1016/j.cell.2018.08.062. PubMed DOI

Yan N., Regalado-Magdos A.D., Stiggelbout B., Lee-Kirsch M.A., Lieberman J. The Cytosolic Exonuclease TREX1 Inhibits the Innate Immune Response to Human Immunodeficiency Virus Type 1. Nat. Immunol. 2010;11:1005–1013. doi: 10.1038/ni.1941. PubMed DOI PMC

Kumar S., Morrison J.H., Dingli D., Poeschla E. HIV-1 Activation of Innate Immunity Depends Strongly on the Intracellular Level of TREX1 and Sensing of Incomplete Reverse Transcription Products. J. Virol. 2018;92 doi: 10.1128/JVI.00001-18. PubMed DOI PMC

Wheeler L.A., Trifonova R.T., Vrbanac V., Barteneva N.S., Liu X., Bollman B., Onofrey L., Mulik S., Ranjbar S., Luster A.D., et al. TREX1 Knockdown Induces an Interferon Response to HIV That Delays Viral Infection in Humanized Mice. Cell Rep. 2016;15:1715–1727. doi: 10.1016/j.celrep.2016.04.048. PubMed DOI PMC

Doitsh G., Cavrois M., Lassen K.G., Zepeda O., Yang Z., Santiago M.L., Hebbeler A.M., Greene W.C. Abortive HIV Infection Mediates CD4 T Cell Depletion and Inflammation in Human Lymphoid Tissue. Cell. 2010;143:789–801. doi: 10.1016/j.cell.2010.11.001. PubMed DOI PMC

Monroe K.M., Yang Z., Johnson J.R., Geng X., Doitsh G., Krogan N.J., Greene W.C. IFI16 DNA Sensor Is Required for Death of Lymphoid CD4 T Cells Abortively Infected with HIV. Science. 2014;343:428–432. doi: 10.1126/science.1243640. PubMed DOI PMC

Dunphy G., Flannery S.M., Almine J.F., Connolly D.J., Paulus C., Jønsson K.L., Jakobsen M.R., Nevels M.M., Bowie A.G., Unterholzner L. Non-Canonical Activation of the DNA Sensing Adaptor STING by ATM and IFI16 Mediates NF-ΚB Signaling after Nuclear DNA Damage. Mol. Cell. 2018;71:745–760.e5. doi: 10.1016/j.molcel.2018.07.034. PubMed DOI PMC

Heiser K., Nicholas C., Garcea R.L. Activation of DNA Damage Repair Pathways by Murine Polyomavirus. Virology. 2016;497:346–356. doi: 10.1016/j.virol.2016.07.028. PubMed DOI PMC

Jiang M., Zhao L., Gamez M., Imperiale M.J. Roles of ATM and ATR-Mediated DNA Damage Responses during Lytic BK Polyomavirus Infection. PLoS Pathog. 2012;8:e1002898. doi: 10.1371/journal.ppat.1002898. PubMed DOI PMC

Sowd G.A., Li N.Y., Fanning E. ATM and ATR Activities Maintain Replication Fork Integrity during SV40 Chromatin Replication. PLoS Pathog. 2013;9:e1003283. doi: 10.1371/journal.ppat.1003283. PubMed DOI PMC

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...