{"doi":"10.3390/pathogens14080815","title":"Relationship Between Cell Surface Viral Glycoprotein Expression and Resistance of Parainfluenza Virus Persistently Infected Cells to Complement-Mediated Lysis","abstract":"Persistent RNA virus infections (PI) are often characterized by extended viral shedding and maintained cycles of inflammation. The innate immune Complement (C') pathways can recognize acute infected (AI) cells and result in their lysis, but the relative sensitivity of PI cells to C'-directed killing is incompletely understood. Here, we extended our previous studies on the interactions of C' with parainfluenza virus AI and PI A549 cells to two additional respiratory tract cell lines. AI Hep2 and H1975 cells infected with Parainfluenza virus 5 (PIV5) were found to be highly sensitive to C' lysis. By contrast, PIV5 PI cells were highly resistant to killing by C″. Surface deposition of membrane attack complex (MAC) and C3 was also greatly reduced on the surface of PI cells compared to AI cells. PI cells had lower levels of surface viral glycoprotein expression compared to AI cells. Treatment of AI cells with ribavirin (RBV) showed a dose-dependent decrease in both viral glycoprotein expression and sensitivity to C'-mediated lysis. When surface viral glycoprotein levels were reduced in AI cells to those in PI cells, AI cells became similarly resistant to C'. While sialic acid levels on PI cell surfaces matched that of naïve cells, enzymatic removal of this sialic acid did not increase sensitivity to C'-mediated lysis. Despite their varying profiles of C' activation and deposition, these studies indicate downregulation of viral gene expression as a common mechanism of C' resistance across various parainfluenza virus PI cell lines.","journal":"Pathogens","year":2025,"id":546118,"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":0.9552,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":599759,"name":"Griffith D. Parks","orcid":"0000-0002-7365-0093","position":1,"is_corresponding":false},{"id":1389680,"name":"Nasser N. Yousef","orcid":null,"position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:53:27.751050Z","pmid":"40872325","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":[]}