PARP10 condensation inhibits viral replication via targeting NAD+ homeostasis

  • Nat Commun. 2026 Sep 26;17(1):11157. doi: 10.1038/s41467-026-78058-y.
Xiaoxin Chen  1  2  3 ,  Qi Xu  2  3 ,  Yi Liu  2  3 ,  Zhenshuo Zhu  2  3 ,  Ziqiu Wang  2  3 ,  Yun Zhang  2  3 ,  Ziru Li  2  3 ,  Yunan Mao  2  3  4 ,  Chenmiao Ai  2  3 ,  Qi Chen  2  3 ,  Le Tian  2  3 ,  Zhiying Yao  2  3 ,  Youngdae Gwon  5 ,  Zhubing Shi  6  7 ,  Peiguo Yang  8  9  10
Affiliations
  • 1. Fudan University, Shanghai, China.
  • 2. State Key Laboratory of Gene Expression & Zhejiang Key Laboratory of Structural Biology, School of Life Sciences, Westlake University, Hangzhou, China.
  • 3. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China.
  • 4. School of Future Biomedicine, Westlake University, Hangzhou, China.
  • 5. Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Republic of Korea.
  • 6. State Key Laboratory of Gene Expression & Zhejiang Key Laboratory of Structural Biology, School of Life Sciences, Westlake University, Hangzhou, China. [email protected].
  • 7. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. [email protected].
  • 8. State Key Laboratory of Gene Expression & Zhejiang Key Laboratory of Structural Biology, School of Life Sciences, Westlake University, Hangzhou, China. [email protected].
  • 9. Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, China. [email protected].
  • 10. School of Future Biomedicine, Westlake University, Hangzhou, China. [email protected].
PMID: 42934229 DOI: 10.1038/s41467-026-78058-y
Abstract

Although diphtheria toxin-like ADP-ribosyltransferases (ARTDs) are implicated in host-virus interactions, the specific Antiviral mechanisms of certain family members remain largely undefined. Here, we reveal that mono-ADP-ribosyltransferase PARP10 restricts viral replication by forming biomolecular condensates via multivalent interactions among its structured domains. PARP10 condensates enhance enzymatic activity, resulting in increased NAD⁺ consumption that ultimately inhibits viral replication. The Antiviral effects of PARP10 are shown to require both its catalytic activity and NAD⁺ regulation, as catalytic mutants and PARP10 inhibitors abrogate these effects, while reduction of NAD⁺ potently restricts viral replication. Furthermore, we identify auto-ADP-ribosylation as an intrinsic negative feedback mechanism modulating PARP10 condensation. These findings establish PARP10 condensation as a compartmentalization strategy that amplifies local NAD⁺ consumption to safeguard host Antiviral immunity.

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