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A new splice variant of the human guanylate‐binding protein 3 mediates anti‐influenza activity through inhibition of viral transcription and replication
Author(s) -
Nordmann Alexandra,
Wixler Ludmilla,
Boergeling Yvonne,
Wixler Viktor,
Ludwig Stephan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-189886
Subject(s) - splice , transcription (linguistics) , virology , viral replication , biology , microbiology and biotechnology , gene , genetics , virus , linguistics , philosophy
Guanylate‐binding proteins (GBPs) belong to the family of large GTPases that are induced in response to interferons. GBPs contain an N‐terminal globular GTPase domain and a C‐terminal α‐helical regulatory domain that are connected by a short middle domain. Antiviral activity against vesicular stomatitis virus and encephalomyocarditis virus has been shown for hGBP‐1; however, no anti‐influenza virus properties for GBPs have been described to date. Here we show that hGBP‐1 and hGBP‐3 possess anti‐influenza viral activity. Furthermore, we have identified a novel splice variant of hGBP‐3, named hGBP‐3ΔC, with a largely modified C‐terminal α‐helical domain. While all three GBP isoforms were up‐regulated on influenza virus infection, hGBP‐3ΔC showed the most prominent antiviral activity in epithelial cells. Mutational analysis of hGBPs revealed that the globular domain is the principal antiviral effector domain, and GTP‐binding, but not hydrolysis, is necessary for antiviral action. Furthermore, we showed that hGBP‐3ΔC strongly represses the activity of the viral polymerase complex, which results in decreased synthesis of viral vRNA, cRNA, mRNA, and viral proteins, as well.—Nordmann, A., Wixler, L., Boergeling, Y., Wixler, V., Ludwig, S. A new splice variant of the human guanylate‐binding protein 3 mediates anti‐influenza activity through inhibition of viral transcription and replication. FASEB J. 26, 1290‐1300 (2012). www.fasebj.org