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Volume 41 Issue 5
October 2026
    Citation: Mingyue Song, Shuyi Wang, Xiao Fei, Guijie Guo. Viral manipulation of DNA damage response signaling: Molecular mechanisms and therapeutic implications .VIROLOGICA SINICA, 2026, 41(5) : 1007-1022.  http://dx.doi.org/10.1016/j.virs.2026.08.014
    shu

    Viral manipulation of DNA damage response signaling: Molecular mechanisms and therapeutic implications

    • a. Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China;

    • b. Joint Laboratory of Animal Pathogen Prevention and Control of Fujian-Nepal, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China;

    • c. Engineering Research Center for Animal Breeding and Sustainable Production, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China

    • The DNA damage response (DDR) network maintains genomic integrity, functions as a signaling hub that viruses exploit to drive pathogenesis, and constitutes a central interface between viral infection and host cell fate. This review discusses the molecular mechanisms by which viruses subvert host DDR pathways, with an emphasis on viral replication, latency, immune evasion, and host genomic instability. Representative examples include PARP1-dependent ccDNA stabilization by hepatitis B virus (HBV), MRN complex sequestration by herpes simplex virus type 1 (HSV-1) for immune evasion, ATM signaling modulation by human immunodeficiency virus (HIV) to maintain viral latency, and DDR activation triggered by RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus (ZIKV), and influenza A virus (IAV) via oxidative stress. We evaluate emerging DDR-targeted antiviral strategies, including restoring intrinsic host restriction, exploiting synthetic lethality of dysregulated DDR kinases, and therapeutically modulating DDR-innate immune crosstalk to restore antiviral surveillance (e.g., by stabilizing MRE11 or inhibiting PARP7). Bridging molecular insights with clinical translation, this review positions DDR targeting as a mechanism-driven, host-directed antiviral paradigm.
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      Viral manipulation of DNA damage response signaling: Molecular mechanisms and therapeutic implications

        Corresponding author: Xiao Fei, xiaofei@fafu.edu.cn
        Corresponding author: Guijie Guo, guojie1125@163.com
      • a. Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China;
      • b. Joint Laboratory of Animal Pathogen Prevention and Control of Fujian-Nepal, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China;
      • c. Engineering Research Center for Animal Breeding and Sustainable Production, College of Animal Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China
      • Received Date: 02 March 2026
      • Accepted Date: 21 August 2026

      Abstract: The DNA damage response (DDR) network maintains genomic integrity, functions as a signaling hub that viruses exploit to drive pathogenesis, and constitutes a central interface between viral infection and host cell fate. This review discusses the molecular mechanisms by which viruses subvert host DDR pathways, with an emphasis on viral replication, latency, immune evasion, and host genomic instability. Representative examples include PARP1-dependent ccDNA stabilization by hepatitis B virus (HBV), MRN complex sequestration by herpes simplex virus type 1 (HSV-1) for immune evasion, ATM signaling modulation by human immunodeficiency virus (HIV) to maintain viral latency, and DDR activation triggered by RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Zika virus (ZIKV), and influenza A virus (IAV) via oxidative stress. We evaluate emerging DDR-targeted antiviral strategies, including restoring intrinsic host restriction, exploiting synthetic lethality of dysregulated DDR kinases, and therapeutically modulating DDR-innate immune crosstalk to restore antiviral surveillance (e.g., by stabilizing MRE11 or inhibiting PARP7). Bridging molecular insights with clinical translation, this review positions DDR targeting as a mechanism-driven, host-directed antiviral paradigm.

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