Viral Modulation of the DNA Damage Response and Innate Immunity: Two Sides of the Same Coin. Issue 6 (30th March 2022)

• Record Type: Journal Article
• Authors: Lopez, Andrew; Nichols Doyle, Randilea; Sandoval, Carina; Nisson, Karly; Yang, Vivian; Fregoso, Oliver I.
• Is Part Of: Journal of molecular biology. Volume 434:Issue 6(2022)
• Publication Date: 2022-03-30
• Subjects: DNA damage response -- innate immunity -- viral-host interactions -- viral replication -- antiviral response; Ad adenovirus -- ATR ataxia telangiectasia and Rad3-related protein -- ATM ataxia-telangiectasia mutated -- cGAS cyclic GMP–AMP synthase -- DDR DNA damage response -- DNA-PK Ku70, Ku80, and DNA-PKcs -- DSB double-stranded DNA break -- dsDNA double-stranded DNA E, early -- EBV Epstein-Barr virus -- HSV herpes simplex virus -- HR homologous recombination -- HEK human embryonic kidney -- HIV human immunodeficiency virus -- HPV human papillomavirus -- HTLV human T-lymphotropic virus -- IBV infectious bronchitis virus -- IAV influenza A -- IFI16 interferon gamma inducible protein 16 -- IRF interferon regulatory factor -- IFN interferon -- KSHV Kaposi's sarcoma-associated herpesvirus -- LANA latency-associated nuclear antigen -- MMR mismatch repair -- MRE11 meiotic recombination 11 MRN, MRE11, Rad50, NBS1 -- NEHJ nonhomologous end joining -- NF-κB nuclear factor kappa B -- PARP1 poly(ADP) ribose polymerase -- PS positive selection -- PTM post-translational modification -- PFGE pulsed-field gel electrophoresis -- RPA replication protein A -- SAMHD1 SAM domain and HD domain-containing protein 1 -- SV40 simian virus 40, SSB, single-strand DNA break -- ssDNA single-stranded DNA -- STING stimulator of interferon genes; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2021.167327
• Languages: English
• ISSNs: 0022-2836

Abstract

Graphical abstract: Highlights: Modulating the DDR is integral to viral replication and evolutionarily conserved by diverse viruses. The DDR can be both beneficial and antiviral. Engagement of the DDR by viruses cause cellular consequences that are interconnected. There is extensive crosstalk between the DDR and innate immunity. The lack of DDR-specific experiments and assays has hindered the ability to move the field forward. Abstract: The DDR consists of multiple pathways that sense, signal, and respond to anomalous DNA. To promote efficient replication, viruses have evolved to engage and even modulate the DDR. In this review, we will discuss a select set of diverse viruses and the range of mechanisms they evolved to interact with the DDR and some of the subsequent cellular consequences. There is a dichotomy in that the DDR can be both beneficial for viruses yet antiviral. We will also review the connection between the DDR and innate immunity. Previously believed to be disparate cellular functions, more recent research is emerging that links these processes. Furthermore, we will discuss some discrepancies in the literature that we propose can be remedied by utilizing more consistent DDR-focused assays. By doing so, we hope to obtain a much clearer understanding of how broadly these mechanisms and phenotypes are conserved among all viruses. This is crucial for human health since understanding how viruses manipulate the DDR presents an important and tractable target for antiviral therapies.