PA-X: a key regulator of influenza A virus pathogenicity and host immune responses

PA-X, a fusion protein belonging to influenza A viruses (IAVs), integrating the N-terminal 191 amino acids of PA gene and the ribosomal frame-shifting product that lengthens out to 41 or 61 amino acids. Since its discovery in 2012, multiple functions have been attributed to this small protein, inclu...

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Bibliographic Details
Published in:Medical microbiology and immunology 2018-11, Vol.207 (5-6), p.255-269
Main Authors: Hu, Jiao, Ma, Chunxi, Liu, Xiufan
Format: Article
Language:English
Subjects:
Amino acids
Animals
Apoptosis
Biomedical and Life Sciences
Biomedicine
Fusion protein
Host-Pathogen Interactions
Humans
Immune Evasion
Immune response
Immunology
Influenza
Influenza A
Influenza A virus - pathogenicity
Influenza A virus - physiology
Localization
Medical Microbiology
Pathogenicity
Pathogens
Protein biosynthesis
Protein Interaction Maps
Protein synthesis
Proteins
Repressor Proteins - metabolism
Review
Viral Nonstructural Proteins - metabolism
Virology
Virulence
Virulence Factors - metabolism
Virus Replication
Viruses
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Description
Summary:PA-X, a fusion protein belonging to influenza A viruses (IAVs), integrating the N-terminal 191 amino acids of PA gene and the ribosomal frame-shifting product that lengthens out to 41 or 61 amino acids. Since its discovery in 2012, multiple functions have been attributed to this small protein, including a process, where wide-spread protein synthesis in infected host cells is shut down (called host shutoff), and viral replication, polymerase activity, viral-induced cell apoptosis, PA nuclear localization, and virulence are modulated. However, many of its proposed functions may be specific to strain, subtype, host, or cell line. In this review, we start by describing the well-defined global host-shutoff ability of PA-X and the potential mechanisms underlying it. We move on to the role played by PA-X in modulating innate and acquired immune responses in the host. We then systematically discuss the role played by PA-X in modulating the virulence of influenza viruses of different subtypes and host origins, and finish with a general overview of the research advances made in identifying the host cell partners that interact with PA-X. To uncover possible clues about the differential effects of PA-X in modulating viral virulence, we focus on systemically evaluating polymorphisms in PA-X from various viral subtypes and hosts, including avian and human H5N1, H5N6, H9N2, and H7N9 viruses. Finally, we conclude with a proposition regarding the possible future research directions for this important protein.
ISSN:0300-8584
1432-1831
DOI:10.1007/s00430-018-0548-z