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Twenty amino acids at the C-terminus of PA-X are associated with increased influenza A virus replication and pathogenicity
- Source :
- The Journal of General Virology
- Publication Year :
- 2015
- Publisher :
- Microbiology Society, 2015.
-
Abstract
- The PA-X protein, arising from ribosomal frameshift during PA translation, was recently discovered in influenza A virus (IAV). The C-terminal domain ‘X’ of PA-X proteins in IAVs can be classified as full-length (61 aa) or truncated (41 aa). In the main, avian influenza viruses express full-length PA-X proteins, whilst 2009 pandemic H1N1 (pH1N1) influenza viruses harbour truncated PA proteins. The truncated form lacks aa 232–252 of the full-length PA-X protein. The significance of PA-X length in virus function remains unclear. To address this issue, we constructed a set of contemporary influenza viruses (pH1N1, avian H5N1 and H9N2) with full and truncated PA-X by reverse genetics to compare their replication and host pathogenicity. All full-length PA-X viruses in human A549 cells conferred 10- to 100-fold increase in viral replication and 5–8 % increase in apoptosis relative to corresponding truncated PA-X viruses. Full-length PA-X viruses were more virulent and caused more severe inflammatory responses in mice. Furthermore, aa 233–252 at the C terminus of PA-X strongly suppressed co-transfected gene expression by ∼50 %, suggesting that these terminal 20 aa could play a role in enhancing viral replication and contribute to virulence.
- Subjects :
- viruses
Amino Acid Motifs
Virulence
Viral Nonstructural Proteins
Biology
Virus Replication
medicine.disease_cause
H5N1 genetic structure
Negative-strand RNA Viruses
Ribosomal frameshift
Virus
Mice
Influenza A Virus, H1N1 Subtype
Virology
Influenza, Human
Influenza A Virus, H9N2 Subtype
medicine
Influenza A virus
Animals
Humans
Mice, Inbred BALB C
Influenza A Virus, H5N1 Subtype
Animal
Standard
Influenza A virus subtype H5N1
Reverse genetics
Repressor Proteins
Viral replication
Female
Subjects
Details
- Language :
- English
- ISSN :
- 00221317
- Database :
- OpenAIRE
- Journal :
- The Journal of General Virology
- Accession number :
- edsair.doi.dedup.....18ab17a4358b7176df0d8def9f8a90f1