TRIM22 inhibits influenza A virus infection by targeting the viral nucleoprotein for degradation

Andrea Di Pietro, Anna Kajaste-Rudnitski, Alexandra Oteiza, Lucia Nicora, Greg J. Towers, Nadir Mechti, Elisa Vicenzi

Research output: Contribution to journalArticle

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Abstract

Tripartite motif (TRIM) protein superfamily members are emerging as important effectors of the innate immune response against viral infections. In particular, TRIM22 was reported to exert antiviral activity against RNA viruses, such as hepatitis B virus (HBV), encephalomyocarditis virus (ECMV), and human immunodeficiency virus type 1 (HIV-1). We demonstrate here, for the first time, that TRIM22 is upregulated by influenza A virus (IAV) infection at both mRNA and protein levels in human alveolar epithelial A549 cells. Conversely, TRIM22 potently restricted IAV replication, in that prevention of TRIM22 expression by means of short hairpin RNA led to a 10-fold enhancement of IAV replication in these cells. Depletion of TRIM22 also reduced the anti-IAV activity of alpha interferon (IFN-α), suggesting that TRIM22 is an important IFN-stimulated gene that is required for maximal suppression of IAV by type I IFN. Furthermore, the IAV infectious titer decreased up to 100-fold in MDCK cells expressing exogenous human TRIM22. Restriction of IAV replication was accounted for by the interaction between TRIM22 and the viral nucleoprotein (NP), resulting in its polyubiquitination and degradation in a proteasome-dependent manner. Thus, TRIM22 represents a novel restriction factor upregulated upon IAV infection that curtails its replicative capacity in epithelial cells.

Original languageEnglish
Pages (from-to)4523-4533
Number of pages11
JournalJournal of Virology
Volume87
Issue number8
DOIs
Publication statusPublished - Apr 2013

Fingerprint

nucleoproteins
Nucleoproteins
Influenza A virus
Virus Diseases
degradation
infection
Virus Replication
virus replication
epithelial cells
Encephalomyocarditis virus
Alveolar Epithelial Cells
interferon-alpha
Madin Darby Canine Kidney Cells
Hepatitis B virus
RNA Viruses
proteasome endopeptidase complex
Proteasome Endopeptidase Complex
small interfering RNA
Human immunodeficiency virus 1
Viral Load

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

TRIM22 inhibits influenza A virus infection by targeting the viral nucleoprotein for degradation. / Di Pietro, Andrea; Kajaste-Rudnitski, Anna; Oteiza, Alexandra; Nicora, Lucia; Towers, Greg J.; Mechti, Nadir; Vicenzi, Elisa.

In: Journal of Virology, Vol. 87, No. 8, 04.2013, p. 4523-4533.

Research output: Contribution to journalArticle

Di Pietro, Andrea ; Kajaste-Rudnitski, Anna ; Oteiza, Alexandra ; Nicora, Lucia ; Towers, Greg J. ; Mechti, Nadir ; Vicenzi, Elisa. / TRIM22 inhibits influenza A virus infection by targeting the viral nucleoprotein for degradation. In: Journal of Virology. 2013 ; Vol. 87, No. 8. pp. 4523-4533.
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