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Open AccessArticle

Global Interactomics Connect Nuclear Mitotic Apparatus Protein NUMA1 to Influenza Virus Maturation

1
Department of Medical Microbiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J6, Canada
2
Manitoba Centre for Proteomics & Systems Biology, Room 799, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
3
Department of Physiology and Pathophysiology, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J6, Canada
4
Genomic Centre for Cancer Research and Diagnosis, Research Institute in Oncology and Hematology, ON6026-675 McDermot Avenue, Winnipeg, MB R3E 0V9, Canada
5
Children’s Hospital Research Institute of Manitoba, Room 513, John Buhler Research Centre, 715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada
*
Author to whom correspondence should be addressed.
Viruses 2018, 10(12), 731; https://doi.org/10.3390/v10120731
Received: 1 October 2018 / Revised: 18 December 2018 / Accepted: 18 December 2018 / Published: 19 December 2018
(This article belongs to the Special Issue CSV2018: The 2nd symposium of the Canadian Society for Virology (CSV))
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. View Full-Text
Keywords: Influenza A virus (IAV); monoclonal antibodies (mAbs); immunoprecipitation (IP), Western blotting; knockdown (KD); siRNA; Nuclear mitotic apparatus protein 1 (NUMA1); Viral replication Influenza A virus (IAV); monoclonal antibodies (mAbs); immunoprecipitation (IP), Western blotting; knockdown (KD); siRNA; Nuclear mitotic apparatus protein 1 (NUMA1); Viral replication
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Rahim, M.N.; Klewes, L.; Zahedi-Amiri, A.; Mai, S.; Coombs, K.M. Global Interactomics Connect Nuclear Mitotic Apparatus Protein NUMA1 to Influenza Virus Maturation. Viruses 2018, 10, 731.

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