PMID- 38257829 OWN - NLM STAT- MEDLINE DCOM- 20240220 LR - 20240220 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 16 IP - 1 DP - 2024 Jan 16 TI - Chloride Intracellular Channel Protein 1 (CLIC1) Is a Critical Host Cellular Factor for Influenza A Virus Replication. LID - 10.3390/v16010129 [doi] LID - 129 AB - (1) Background: Influenza A Virus (IAV) uses host cellular proteins during replication in host cells. IAV infection causes elevated expression of chloride intracellular channel protein 1 (CLIC1) in lung epithelial cells, but the importance of this protein in IAV replication is unknown. (2) In this study, we determined the role of CLIC1 in IAV replication by investigating the effects of CLIC1 knockdown (KD) on IAV viral protein translation, genomic RNA transcription, and host cellular proteome dysregulation. (3) Results: CLIC1 KD in A549 human lung epithelial cells resulted in a significant decrease in progeny supernatant IAV, but virus protein expression was unaffected. However, a significantly larger number of viral RNAs accumulated in CLIC1 KD cells. Treatment with a CLIC1 inhibitor also caused a significant reduction in IAV replication, suggesting that CLIC1 is an important host factor in IAV replication. SomaScan((R)), which measures 1322 proteins, identified IAV-induced dysregulated proteins in wild-type cells and in CLIC1 KD cells. The expression of 116 and 149 proteins was significantly altered in wild-type and in CLIC1 KD cells, respectively. A large number of the dysregulated proteins in CLIC1 KD cells were associated with cellular transcription and predicted to be inhibited during IAV replication. (4) Conclusions: This study suggests that CLIC1 is involved in later stages of IAV replication. Further investigation should clarify mechanism(s) for the development of anti-IAV drugs targeting CLIC1 protein. FAU - Rashid, Mahamud-Ur AU - Rashid MU AUID- ORCID: 0000-0002-3785-2122 AD - Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Room 543 Basic Medical Sciences Building, 745 Bannatyne Avenue, Winnipeg, MB R3E OJ9, Canada. AD - Manitoba Centre for Proteomics and Systems Biology, Room 799, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada. FAU - Coombs, Kevin M AU - Coombs KM AD - Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Room 543 Basic Medical Sciences Building, 745 Bannatyne Avenue, Winnipeg, MB R3E OJ9, Canada. AD - Manitoba Centre for Proteomics and Systems Biology, Room 799, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada. AD - Children's Hospital Research Institute of Manitoba, Room 513, John Buhler Research Centre, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada. LA - eng GR - MOP-106713/CAPMC/CIHR/Canada PT - Journal Article DEP - 20240116 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Chloride Channels) RN - 0 (CLIC1 protein, human) RN - 0 (RNA, Viral) SB - IM MH - Humans MH - *Chloride Channels/genetics MH - *Influenza A virus/physiology MH - *Influenza, Human MH - RNA, Viral MH - *Virus Replication PMC - PMC10819074 OTO - NOTNLM OT - CLIC1 OT - NPPB OT - host factor OT - influenza A virus OT - replication cycle OT - transcription COIS- The authors declare no conflicts of interest. EDAT- 2024/01/23 06:43 MHDA- 2024/01/24 06:44 PMCR- 2024/01/16 CRDT- 2024/01/23 01:23 PHST- 2023/11/25 00:00 [received] PHST- 2024/01/10 00:00 [revised] PHST- 2024/01/13 00:00 [accepted] PHST- 2024/01/24 06:44 [medline] PHST- 2024/01/23 06:43 [pubmed] PHST- 2024/01/23 01:23 [entrez] PHST- 2024/01/16 00:00 [pmc-release] AID - v16010129 [pii] AID - viruses-16-00129 [pii] AID - 10.3390/v16010129 [doi] PST - epublish SO - Viruses. 2024 Jan 16;16(1):129. doi: 10.3390/v16010129.