{"doi":"10.1128/jvi.00426-07","title":"Protein Kinase PKR Plays a Stimulus- and Virus-Dependent Role in Apoptotic Death and Virus Multiplication in Human Cells","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>The protein kinase regulated by double-stranded RNA (dsRNA), PKR, is implicated in a range of biologic processes, including apoptotic death and interferon antiviral responses, based in part on studies with mouse cells genetically deficient in<jats:italic>Pkr</jats:italic>. To test the role of the PKR protein in human cells, an RNA interference silencing strategy was used to generate stable HeLa cell lines with less than 2% of the PKR protein (PKR deficient) compared to either parental or control knockdown HeLa lines. Phosphorylation of the α subunit of eukaryotic initiation factor 2 on serine 51 was not detectably increased in response to dsRNA in PKR-deficient HeLa cells but was elevated severalfold in PKR-sufficient cells. PKR-deficient cells displayed reduced dsRNA-induced apoptosis compared to PKR-sufficient cell lines, whereas tumor necrosis factor alpha (TNF-α)-induced apoptosis was comparable between the HeLa lines. NF-κB was activated to a comparable extent in PKR-deficient and PKR-sufficient HeLa cells upon treatment with either dsRNA or TNF-α. The antiviral response against vesicular stomatitis virus was reduced in interferon-treated PKR-deficient compared to PKR-sufficient HeLa cells. However, the growth of two human viruses, adenovirus and reovirus, was unaffected by the PKR knockdown. Surprisingly, the yield of mutant adenovirus that fails to encode VAI RNA was not enhanced in PKR-deficient cells, indicating the importance of host factors in addition to PKR in conferring the VAI RNA phenotype.</jats:p>","journal":"Journal of Virology","year":2007,"id":21926,"datarank":3.236175633197854,"base_score":4.634728988229636,"endowment":4.634728988229636,"self_citation_contribution":0.6952093482344455,"citation_network_contribution":2.5409662849634085,"self_endowment_contribution":0.6952093482344455,"citer_contribution":2.5409662849634085,"corpus_percentile":null,"corpus_rank":null,"citation_count":102,"citer_count":76,"citers_with_citation_signal":63,"citers_with_endowment":63,"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":136425,"name":"Charles E. Samuel","orcid":null,"position":1,"is_corresponding":false},{"id":52428,"name":"Ping Zhang","orcid":"0000-0001-9163-6191","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.634728988229636,"endowment":4.634728988229636,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17522227","pmcid":"PMC1951329","openalex_id":"https://openalex.org/W2156083701","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI020611","title":null}],"total_grants":1,"fwci":3.3635,"citation_percentile":0.93022608,"influential_citations":3,"citation_trend":[{"year":2012,"count":8},{"year":2013,"count":8},{"year":2014,"count":4},{"year":2015,"count":3},{"year":2016,"count":5},{"year":2017,"count":1},{"year":2018,"count":4},{"year":2019,"count":8},{"year":2020,"count":4},{"year":2021,"count":6},{"year":2022,"count":2},{"year":2023,"count":1},{"year":2024,"count":7},{"year":2025,"count":9}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1951329","host_type":"repository"},{"url":"https://europepmc.org/articles/pmc1951329?pdf=render","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1951329","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.00426-07","host_type":"publisher"},{"url":"https://doi.org/10.1128/jvi.00426-07","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17522227","host_type":"repository"},{"url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.529.7643","host_type":""}],"fields_of_study":["RNA regulation and disease","RNA Interference and Gene Delivery","interferon and immune responses","Medicine","Biology","Animals","Apoptosis","Eukaryotic Initiation Factor-2","Gene Silencing","HeLa Cells","Humans","Mice","Mice, Knockout","NF-kappa B","Phosphorylation","Poly(ADP-ribose) Polymerases","RNA","RNA, Double-Stranded","Signal Transduction","Tumor Necrosis Factor-alpha","Virus Replication","eIF-2 Kinase"],"mesh_terms":["Animals","HeLa Cells","Humans","Phosphorylation","Poly(ADP-ribose) Polymerases","RNA","RNA, Double-Stranded","Tumor Necrosis Factor-alpha","Virus Replication","Signal Transduction","Eukaryotic Initiation Factor-2","NF-kappa B","Apoptosis","Mice, Knockout","eIF-2 Kinase","Gene Silencing","Mice","Hela Cells"],"keywords":["Protein kinase R","EIF-2 kinase","Biology","HeLa","Interferon","RNA silencing","Molecular biology","Protein kinase A","Gene knockdown","Virology","RNA","Cell culture","Vesicular stomatitis virus","RNA interference","Cell biology","Virus","Kinase","Mitogen-activated protein kinase kinase","Biochemistry","Cyclin-dependent kinase 2","Genetics","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-06T17:17:41.633484Z","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":[]}