PMID- 30572664 OWN - NLM STAT- MEDLINE DCOM- 20190415 LR - 20201209 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 10 IP - 12 DP - 2018 Dec 19 TI - Global Interactomics Connect Nuclear Mitotic Apparatus Protein NUMA1 to Influenza Virus Maturation. LID - 10.3390/v10120731 [doi] LID - 731 AB - Influenza A virus (IAV) infections remain a major human health threat. IAV has enormous genetic plasticity and can rapidly escape virus-targeted anti-viral strategies. Thus, there is increasing interest to identify host proteins and processes the virus requires for replication and maturation. The IAV non-structural protein 1 (NS1) is a critical multifunctional protein that is expressed to high levels in infected cells. Host proteins that interact with NS1 may serve as ideal targets for attenuating IAV replication. We previously developed and characterized broadly cross-reactive anti-NS1 monoclonal antibodies. For the current study, we used these mAbs to co-immunoprecipitate native IAV NS1 and interacting host proteins; 183 proteins were consistently identified in this NS1 interactome study, 124 of which have not been previously reported. RNAi screens identified 11 NS1-interacting host factors as vital for IAV replication. Knocking down one of these, nuclear mitotic apparatus protein 1 (NUMA1), dramatically reduced IAV replication. IAV genomic transcription and translation were not inhibited but transport of viral structural proteins to the cell membrane was hindered during maturation steps in NUMA1 knockdown (KD) cells. FAU - Rahim, Md Niaz AU - Rahim MN AUID- ORCID: 0000-0003-2042-134X AD - Department of Medical Microbiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J6, Canada. mdniaz.rahim@canada.ca. AD - Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada. mdniaz.rahim@canada.ca. FAU - Klewes, Ludger AU - Klewes L AD - Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J6, Canada. Ludger.Klewes@umanitoba.ca. AD - Genomic Centre for Cancer Research and Diagnosis, Research Institute in Oncology and Hematology, ON6026-675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada. Ludger.Klewes@umanitoba.ca. FAU - Zahedi-Amiri, Ali AU - Zahedi-Amiri A AD - Department of Medical Microbiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J6, Canada. zahediaa@myumanitoba.ca. AD - Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada. zahediaa@myumanitoba.ca. FAU - Mai, Sabine AU - Mai S AUID- ORCID: 0000-0002-5797-2201 AD - Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J6, Canada. Sabine.Mai@umanitoba.ca. AD - Genomic Centre for Cancer Research and Diagnosis, Research Institute in Oncology and Hematology, ON6026-675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada. Sabine.Mai@umanitoba.ca. FAU - Coombs, Kevin M AU - Coombs KM AD - Department of Medical Microbiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J6, Canada. Kevin.Coombs@umanitoba.ca. AD - Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada. Kevin.Coombs@umanitoba.ca. AD - Children's Hospital Research Institute of Manitoba, Room 513, John Buhler Research Centre, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada. Kevin.Coombs@umanitoba.ca. LA - eng GR - MOP-106713/CIHR/Canada GR - PAN-83159/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181219 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Antigens, Nuclear) RN - 0 (Cell Cycle Proteins) RN - 0 (NUMA1 protein, human) RN - 0 (Nuclear Matrix-Associated Proteins) RN - 0 (Viral Nonstructural Proteins) SB - IM MH - A549 Cells MH - Antigens, Nuclear/genetics/*metabolism MH - Cell Cycle Proteins MH - Cell Line MH - Gene Knockdown Techniques MH - *Host-Pathogen Interactions MH - Humans MH - Immunoprecipitation MH - Influenza A virus/genetics/*physiology MH - Nuclear Matrix-Associated Proteins/genetics/*metabolism MH - RNA Interference MH - Viral Nonstructural Proteins/genetics/*metabolism MH - *Virus Assembly MH - Virus Replication PMC - PMC6316800 OTO - NOTNLM OT - Influenza A virus (IAV) OT - Nuclear mitotic apparatus protein 1 (NUMA1) OT - Viral replication OT - immunoprecipitation (IP), Western blotting OT - knockdown (KD) OT - monoclonal antibodies (mAbs) OT - siRNA COIS- The authors declare that they have no conflict of interest. EDAT- 2018/12/24 06:00 MHDA- 2019/04/16 06:00 PMCR- 2018/12/01 CRDT- 2018/12/22 06:00 PHST- 2018/10/01 00:00 [received] PHST- 2018/12/18 00:00 [revised] PHST- 2018/12/18 00:00 [accepted] PHST- 2018/12/22 06:00 [entrez] PHST- 2018/12/24 06:00 [pubmed] PHST- 2019/04/16 06:00 [medline] PHST- 2018/12/01 00:00 [pmc-release] AID - v10120731 [pii] AID - viruses-10-00731 [pii] AID - 10.3390/v10120731 [doi] PST - epublish SO - Viruses. 2018 Dec 19;10(12):731. doi: 10.3390/v10120731.