Interaction of Host Nucleolin with Influenza A Virus Nucleoprotein in the Early Phase of Infection Limits the Late Viral Gene Expression

Influenza A virus nucleoprotein, is a multifunctional RNA-binding protein, encoded by segment-5 of the negative sense RNA genome. It serves as a key connector between the virus and the host during virus replication. It continuously shuttles between the cytoplasm and the nucleus interacting with vari...

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Bibliographic Details
Published in:PloS one 2016-10, Vol.11 (10), p.e0164146-e0164146
Main Authors: Kumar, Deepshikha, Broor, Shobha, Rajala, Maitreyi S
Format: Article
Language:English
Subjects:
Analysis
Animals
Biology and Life Sciences
Biotechnology
Cell Line, Tumor
Cytoplasm
Dogs
Gene expression
Gene Expression Regulation, Viral
Genes
Genomes
Genomics
Health aspects
Hemagglutinins
Hepatitis
Humans
Immunoprecipitation
Infections
Influenza
Influenza A
Influenza A Virus, H1N1 Subtype - genetics
Influenza A Virus, H1N1 Subtype - metabolism
Influenza A Virus, H1N1 Subtype - physiology
Influenza, Human - epidemiology
Influenza, Human - metabolism
Influenza, Human - virology
Life cycle engineering
Life cycles
Madin Darby Canine Kidney Cells
Medicine and Health Sciences
Nuclei
Nuclei (cytology)
Nucleocapsid Proteins
Nucleoli
Nucleolin
Pandemics
Phosphoproteins - deficiency
Phosphoproteins - genetics
Phosphoproteins - metabolism
Protein Binding
Proteins
Ribonucleic acid
RNA
RNA Interference
RNA, Small Interfering - genetics
RNA-binding protein
RNA-Binding Proteins - genetics
RNA-Binding Proteins - metabolism
Seasons
siRNA
Transcription, Genetic
Viral Core Proteins - genetics
Viral Core Proteins - metabolism
Viral proteins
Virology
Viruses
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Description
Summary:Influenza A virus nucleoprotein, is a multifunctional RNA-binding protein, encoded by segment-5 of the negative sense RNA genome. It serves as a key connector between the virus and the host during virus replication. It continuously shuttles between the cytoplasm and the nucleus interacting with various host cellular factors. In the current study, host proteins interacting with nucleoprotein of Influenza A virus of H1N1 2009 pandemic strain were identified by co-immunoprecipitation studies followed by MALDI-TOF/MS analysis. Here we report the host nucleolin, a major RNA-binding protein of the nucleolus as a novel interacting partner to influenza A virus nucleoprotein. We thus, explored the implications of this interaction in virus life cycle and our studies have shown that these two proteins interact early during infection in the cytoplasm of infected cells. Depletion of nucleolin in A549 cells by siRNA targeting endogenous nucleolin followed by influenza A virus infection, disrupted its interaction with viral nucleoprotein, resulting in increased expression of gene transcripts encoding late viral proteins; matrix (M1) and hemagglutinin (HA) in infected cells. On the contrary, over expression of nucleolin in cells transiently transfected with pEGFP-NCL construct followed by virus infection significantly reduced the late viral gene transcripts, and consequently the viral titer. Altered expression of late viral genes and titers following manipulation of host cellular nucleolin, proposes the functional importance of its interaction with nucleoprotein during influenza A virus infection.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0164146