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Functional Analysis of GRSF1 in the Nuclear Export and Translation of Influenza A Virus mRNAs.
- Source :
-
Viruses [Viruses] 2024 Jul 16; Vol. 16 (7). Date of Electronic Publication: 2024 Jul 16. - Publication Year :
- 2024
-
Abstract
- Influenza A viruses (IAV) utilize host proteins throughout their life cycle to infect and replicate in their hosts. We previously showed that host adaptive mutations in avian IAV PA help recruit host protein G-Rich RNA Sequence Binding Factor 1 (GRSF1) to the nucleoprotein (NP) 5' untranslated region (UTR), leading to the enhanced nuclear export and translation of NP mRNA. In this study, we evaluated the impact of GRSF1 in the viral life cycle. We rescued and characterized a 2009 pH1N1 virus with a mutated GRSF1 binding site in the 5' UTR of NP mRNA. Mutant viral growth was attenuated relative to pH1N1 wild-type (WT) in mammalian cells. We observed a specific reduction in the NP protein production and cytosolic accumulation of NP mRNAs, indicating a critical role of GRSF1 in the nuclear export of IAV NP mRNAs. Further, in vitro-transcribed mutated NP mRNA was translated less efficiently than WT NP mRNA in transfected cells. Together, these findings show that GRSF1 binding is important for both mRNA nuclear export and translation and affects overall IAV growth. Enhanced association of GRSF1 to NP mRNA by PA mutations leads to rapid virus growth, which could be a key process of mammalian host adaptation of IAV.
- Subjects :
- Humans
Animals
Influenza A virus genetics
Influenza A virus physiology
Influenza A virus metabolism
Virus Replication
Influenza A Virus, H1N1 Subtype genetics
Influenza A Virus, H1N1 Subtype metabolism
Influenza A Virus, H1N1 Subtype physiology
Cell Nucleus metabolism
Cell Nucleus virology
5' Untranslated Regions genetics
Nucleocapsid Proteins metabolism
Nucleocapsid Proteins genetics
Madin Darby Canine Kidney Cells
HEK293 Cells
RNA-Binding Proteins metabolism
RNA-Binding Proteins genetics
Dogs
Influenza, Human virology
Influenza, Human metabolism
Influenza, Human genetics
Mutation
Host-Pathogen Interactions genetics
Viral Core Proteins metabolism
Viral Core Proteins genetics
Active Transport, Cell Nucleus
RNA, Messenger genetics
RNA, Messenger metabolism
Protein Biosynthesis
RNA, Viral genetics
RNA, Viral metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1999-4915
- Volume :
- 16
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Viruses
- Publication Type :
- Academic Journal
- Accession number :
- 39066299
- Full Text :
- https://doi.org/10.3390/v16071136