{"doi":"10.1101/2022.10.03.510601","title":"Inhibition of CHK2 dependent DNA damage response suppresses Zika virus infection through a STING dependent mechanism","abstract":"ABSTRACT Zika virus (ZIKV) is a mosquito-borne flavivirus that causes neurological disorders and microcephaly. Recent research has shown that ZIKV causes cell cycle arrest and DNA damage response in neuronal progenitor cells that potentially leads to congenital neurodevelopmental defects. However, the specific role of regulators that control DNA damage response to ZIKV infection and the related mechanisms remain largely unknown. Here through both in vitro and in vivo studies, we observe that ZIKV induces DNA damage response in both human cell line and mouse embryo. When CHK2 dependent DNA damage response pathway is inhibited by a small molecule inhibitor or genetic deletion, ZIKV production is reduced and the embryonic developmental defects are rescued. Furthermore, we demonstrate that in ZIKV infected Chk2-/- mice, the reduced viral load correlates with elevated antiviral innate immune response which is found to be dependent on the STING signaling pathway. Collectively, our study reveals a specific role of CHK2 for ZIKV infection and pathogenesis, demonstrating a mechanism that inhibition of the CHK2 axis suppresses ZIKV infection through the STING-dependent antiviral pathway, thus providing a new therapeutic strategy against ZIKV. These findings also suggest the intriguing possibility that ZIKV evolved to orchestrate DNA damage response factors to create a beneficial environment for its infection in the host cells.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":312135,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":447823,"name":"Chunfeng Li","orcid":"0000-0001-8883-9078","position":1,"is_corresponding":false},{"id":839332,"name":"Yanli Wang","orcid":"0000-0001-5661-4288","position":2,"is_corresponding":false},{"id":840708,"name":"Erika V. Valore","orcid":null,"position":3,"is_corresponding":false},{"id":617007,"name":"Meera Trisal","orcid":null,"position":4,"is_corresponding":false},{"id":989541,"name":"Harold Hui","orcid":"0000-0002-9701-9570","position":5,"is_corresponding":false},{"id":611746,"name":"Paul Hakimpour","orcid":null,"position":6,"is_corresponding":false},{"id":565865,"name":"J. Richard Bowen","orcid":"0000-0003-3498-4207","position":7,"is_corresponding":false},{"id":37427,"name":"Tak W. Mak","orcid":"0000-0001-6766-861X","position":8,"is_corresponding":false},{"id":106937,"name":"Mehul S. Suthar","orcid":"0000-0002-2686-8380","position":9,"is_corresponding":false},{"id":106177,"name":"Bali Pulendran","orcid":"0000-0001-6517-4333","position":10,"is_corresponding":false},{"id":290263,"name":"Huailiang Ma","orcid":null,"position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T00:33:36.072096Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}