{"doi":"10.17615/vfv2-7258","title":"Human Parainfluenza Virus Type 1 C Proteins Are Nonessential Proteins That Inhibit the Host Interferon and Apoptotic Responses and Are Required for Efficient Replication in Nonhuman Primates","abstract":"Recombinant human parainfluenza virus type 1 (rHPIV1) was modified to create rHPIV1-P(C−), a virus in which expression of the C proteins (C′, C, Y1, and Y2) was silenced without affecting the amino acid sequence of the P protein. Infectious rHPIV1-P(C−) was readily recovered from cDNA, indicating that the four C proteins were not essential for virus replication. Early during infection in vitro, rHPIV1-P(C−) replicated as efficiently as wild-type (wt) HPIV1, but its titer subsequently decreased coincident with the onset of an extensive cytopathic effect not observed with wt rHPIV1. rHPIV1-P(C−) infection, but not wt rHPIV1 infection, induced caspase 3 activation and nuclear fragmentation in LLC-MK2 cells, identifying the HPIV1 C proteins as inhibitors of apoptosis. In contrast to wt rHPIV1, rHPIV1-P(C−) and rHPIV1-CF170S, a mutant encoding an F170S substitution in C, induced interferon (IFN) and did not inhibit IFN signaling in vitro. However, only rHPIV1-P(C−) induced apoptosis. Thus, the anti-IFN and antiapoptosis activities of HPIV1 were separable: both activities are disabled in rHPIV1-P(C−), whereas only the anti-IFN activity is disabled in rHPIV1-CF170S. In African green monkeys (AGMs), rHPIV1-P(C−) was considerably more attenuated than rHPIV1-CF170S, suggesting that disabling the anti-IFN and antiapoptotic activities of HPIV1 had additive effects on attenuation in vivo. Although rHPIV1-P(C−) protected against challenge with wt HPIV1, its highly restricted replication in AGMs and in primary human airway epithelial cell cultures suggests that it might be overattenuated for use as a vaccine. Thus, the C proteins of HPIV1 are nonessential but have anti-IFN and antiapoptosis activities required for virulence in primates.","journal":"UNC Libraries","year":2020,"id":117314,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":294659,"name":"Jim Boonyaratanakornkit","orcid":"0000-0001-5858-2662","position":1,"is_corresponding":false},{"id":544943,"name":"A. C. Schmidt","orcid":null,"position":2,"is_corresponding":false},{"id":438785,"name":"R. J. Pickles","orcid":null,"position":3,"is_corresponding":false},{"id":438786,"name":"P. L. Collins","orcid":null,"position":4,"is_corresponding":false},{"id":547633,"name":"A.-M. Cruz","orcid":null,"position":5,"is_corresponding":false},{"id":547634,"name":"J. Esker","orcid":null,"position":6,"is_corresponding":false},{"id":547635,"name":"A. Castano","orcid":null,"position":7,"is_corresponding":false},{"id":547636,"name":"H. Schomacker","orcid":null,"position":8,"is_corresponding":false},{"id":544941,"name":"E. J. Bartlett","orcid":null,"position":9,"is_corresponding":false},{"id":547637,"name":"S. R. Surman","orcid":null,"position":10,"is_corresponding":false},{"id":544942,"name":"B. R. Murphy","orcid":null,"position":11,"is_corresponding":false},{"id":544940,"name":"M. Hennessey","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:13:51.309289Z","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":[]}