Influenza A viral nucleoprotein interacts with cytoskeleton scaffolding protein α-actinin-4 for viral replication

التفاصيل البيبلوغرافية
العنوان: Influenza A viral nucleoprotein interacts with cytoskeleton scaffolding protein α-actinin-4 for viral replication
المؤلفون: John B. Bowzard, Ruben O. Donis, Sunil K. Lal, Nancy J. Cox, Pratibha Gaur, Humaira Farooqi, Renu B. Lal, Shipra Sharma, Jacqueline M. Katz, Adarsh K. Mayank, Suryaprakash Sambhara, Shashank Tripathi, Jenish R. Patel, Himani Nailwal
المصدر: The Febs Journal
بيانات النشر: Wiley, 2014.
سنة النشر: 2014
مصطلحات موضوعية: Transcriptional Activation, Viral protein, viruses, interaction, RNA-binding protein, macromolecular substances, Biology, Virus Replication, medicine.disease_cause, Biochemistry, influenza virus, localization, Virus, Protein Interaction Mapping, Influenza A virus, medicine, Humans, Gene silencing, Actinin, Molecular Biology, nucleoprotein, Ribonucleoprotein, Viral Core Proteins, RNA-Binding Proteins, Original Articles, Cell Biology, Nucleocapsid Proteins, Virology, actinin‐4, Nucleoprotein, Protein Transport, HEK293 Cells, Viral replication, Host-Pathogen Interactions, Original Article
الوصف: Influenza A virus (IAV), similar to other viruses, exploits the machinery of human host cells for its survival and replication. We identified α‐actinin‐4, a host cytoskeletal protein, as an interacting partner of IAV nucleoprotein (NP). We confirmed this interaction using co‐immunoprecipitation studies, first in a coupled in vitro transcription‐translation assay and then in cells either transiently co‐expressing the two proteins or infected with whole IAV. Importantly, the NP–actinin‐4 interaction was observed in several IAV subtypes, including the 2009 H1N1 pandemic virus. Moreover, immunofluorescence studies revealed that both NP and actinin‐4 co‐localized largely around the nucleus and also in the cytoplasmic region of virus‐infected A549 cells. Silencing of actinin‐4 expression resulted in not only a significant decrease in NP, M2 and NS1 viral protein expression, but also a reduction of both NP mRNA and viral RNA levels, as well as viral titers, 24 h post‐infection with IAV, suggesting that actinin‐4 was critical for viral replication. Furthermore, actinin‐4 depletion reduced the amount of NP localized in the nucleus. Treatment of infected cells with wortmannin, a known inhibitor of actinin‐4, led to a decrease in NP mRNA levels and also caused the nuclear retention of NP, further strengthening our previous observations. Taken together, the results of the present study indicate that actinin‐4, a novel interacting partner of IAV NP, plays a crucial role in viral replication and this interaction may participate in nuclear localization of NP and/or viral ribonucleoproteins. Structured digital abstract •http://www.uniprot.org/uniprot/P03466Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915Test with http://www.uniprot.org/uniprot/O43707Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0006Test (http://www.ebi.ac.uk/intact/interaction/EBI-9512541Test, http://www.ebi.ac.uk/intact/interaction/EBI-9512553Test)•http://www.uniprot.org/uniprot/Q8JR21Test and http://www.uniprot.org/uniprot/O43707Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0403Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0416Test (http://www.ebi.ac.uk/intact/interaction/EBI-9514040Test)•http://www.uniprot.org/uniprot/Q91U50Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915Test with http://www.uniprot.org/uniprot/O43707Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0006Test (http://www.ebi.ac.uk/intact/interaction/EBI-9514006Test)•http://www.uniprot.org/uniprot/Q5L4H4Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0407Test to http://www.uniprot.org/uniprot/O43707Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0007Test (http://www.ebi.ac.uk/intact/interaction/EBI-9512166Test, http://www.ebi.ac.uk/intact/interaction/EBI-9512219Test)•http://www.uniprot.org/uniprot/C3W6D7Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915Test with http://www.uniprot.org/uniprot/O43707Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0006Test (http://www.ebi.ac.uk/intact/interaction/EBI-9513951Test)•http://www.uniprot.org/uniprot/Q5L4H4Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915Test with http://www.uniprot.org/uniprot/O43707Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0007Test (http://www.ebi.ac.uk/intact/interaction/EBI-9512237Test)•http://www.uniprot.org/uniprot/Q6DPG0Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915Test with http://www.uniprot.org/uniprot/O43707Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0006Test (http://www.ebi.ac.uk/intact/interaction/EBI-9513984Test) •http://www.uniprot.org/uniprot/B2BU63Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915Test with http://www.uniprot.org/uniprot/O43707Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0006Test (http://www.ebi.ac.uk/intact/interaction/EBI-9513930Test) •http://www.uniprot.org/uniprot/Q5L4H4Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915Test with http://www.uniprot.org/uniprot/O43707Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0018Test (http://www.ebi.ac.uk/intact/interaction/EBI-9512145Test, http://www.ebi.ac.uk/intact/interaction/EBI-9512095Test) •http://www.uniprot.org/uniprot/C9S3S8Test http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0915Test with http://www.uniprot.org/uniprot/O43707Test by http://www.ebi.ac.uk/ontology-lookup/?termId=MI:0006Test (http://www.ebi.ac.uk/intact/interaction/EBI-9513909Test)
Human host proteins aiding the influenza A viral nucleoprotein in replication and transcription of virus and its intracellular shuttling are not well studied. The study presented here reports the dynamics of interaction between NP and actinin‐4 and the pivotal role of cytoskeletal protein in not only trafficking of NP, but also boosting its mRNA and vRNA levels, ultimately elevating viral titers.
تدمد: 1742-464X
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24a0bfc3c55e5b7288a9dff1880bad29Test
https://doi.org/10.1111/febs.12828Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....24a0bfc3c55e5b7288a9dff1880bad29
قاعدة البيانات: OpenAIRE