{"doi":"10.1073/pnas.2111266118","title":"Shiftless inhibits flavivirus replication in vitro and is neuroprotective in a mouse model of Zika virus pathogenesis","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>\n                    Flaviviruses are significant human pathogens and emerging infectious disease threats. A screen of interferon-inducible genes revealed Shiftless (SHFL) as a potent antiviral effector, inhibiting all\n                    <jats:italic>Flaviviridae</jats:italic>\n                    tested, including West Nile, Zika, dengue, yellow fever, and hepatitis C viruses. Mechanistic studies showed that SHFL inhibits viral replication at a point after translation of the incoming genome. In whole-body\n                    <jats:italic>Shfl</jats:italic>\n                    knockout (KO) mice, compared to wild-type mice, the\n                    <jats:italic>Shfl</jats:italic>\n                    KO mice were more susceptible to Zika virus. Notably,\n                    <jats:italic>Shfl</jats:italic>\n                    was uniquely required for controlling replication in the brain and spinal cord, demonstrating an unappreciated neuroprotective role for this effector in vivo. SHFL is a key antiviral effector that specifically inhibits flavivirus genome replication, and\n                    <jats:italic>Shfl</jats:italic>\n                    protects mice from Zika virus–induced neuropathogenesis.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2021,"id":643826,"datarank":0.519860385419959,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"self_citation_contribution":0.519860385419959,"citation_network_contribution":0.0,"self_endowment_contribution":0.519860385419959,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":31,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":241069,"name":"Katrina B. 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Hanners","orcid":"0000-0002-3391-4197","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Shiftless inhibits flavivirus replication in vitro and is neuroprotective in a mouse model of Zika virus pathogenesis","abstract":"<jats:title>Significance</jats:title>\n                  <jats:p>\n                    Flaviviruses are significant human pathogens and emerging infectious disease threats. A screen of interferon-inducible genes revealed Shiftless (SHFL) as a potent antiviral effector, inhibiting all\n                    <jats:italic>Flaviviridae</jats:italic>\n                    tested, including West Nile, Zika, dengue, yellow fever, and hepatitis C viruses. Mechanistic studies showed that SHFL inhibits viral replication at a point after translation of the incoming genome. In whole-body\n                    <jats:italic>Shfl</jats:italic>\n                    knockout (KO) mice, compared to wild-type mice, the\n                    <jats:italic>Shfl</jats:italic>\n                    KO mice were more susceptible to Zika virus. Notably,\n                    <jats:italic>Shfl</jats:italic>\n                    was uniquely required for controlling replication in the brain and spinal cord, demonstrating an unappreciated neuroprotective role for this effector in vivo. SHFL is a key antiviral effector that specifically inhibits flavivirus genome replication, and\n                    <jats:italic>Shfl</jats:italic>\n                    protects mice from Zika virus–induced neuropathogenesis.\n                  </jats:p>","is_dataset_classified":null,"base_score":3.4657359027997265,"endowment":3.4657359027997265,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34873063","pmcid":"PMC8670505","openalex_id":"https://openalex.org/W4200546896","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"T32 AI005284","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"U01 HG004080","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"DP2 AI117922","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"K08 AI132751","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"DP1 AI158124","title":null},{"funder_name":"NHGRI NIH HHS","grant_id":"U01 HG004085","title":null},{"funder_name":"NCRR NIH HHS","grant_id":"U42 RR024244","title":null}],"total_grants":7,"fwci":3.9882,"citation_percentile":0.94149386,"influential_citations":0,"citation_trend":[{"year":2022,"count":7},{"year":2023,"count":9},{"year":2024,"count":5},{"year":2025,"count":7},{"year":2026,"count":3}],"oa_status":"green","license":"https://www.pnas.org/site/aboutpnas/licenses.xhtml","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8670505","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8670505","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.2111266118","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.2111266118","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34873063","host_type":"repository"}],"fields_of_study":["Mosquito-borne diseases and control","Viral Infections and Vectors","Malaria Research and Control","Animals","Cell Line","Cytopathogenic Effect, Viral","Disease Models, Animal","Disease Susceptibility","Flavivirus","Flavivirus Infections","Male","Mice","Mice, Inbred C57BL","Mice, Knockout","Neuroprotective Agents","RNA-Binding Proteins","Virus Replication","Zika Virus","Zika Virus Infection"],"mesh_terms":["Zika Virus Infection","Zika Virus","Animals","Cell Line","Cytopathogenic Effect, Viral","Disease Models, Animal","Disease Susceptibility","Flavivirus","Male","Mice, Inbred C57BL","Virus Replication","RNA-Binding Proteins","Flavivirus Infections","Mice, Knockout","Neuroprotective Agents","Mice"],"keywords":["Flavivirus","Virology","Biology","Viral replication","Zika virus","Interferon","Virus","Neuroprotection","Flaviviridae","Viral pathogenesis","Dengue virus","Effector","Dengue fever","Hepatitis C virus","Immunology","Type I interferon","Pathophysiology","Flaviviruses","Neurotropic Viruses"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"hpa"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T19:08:26.369372Z","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":[]}