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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

A new splice variant of the human guanylate‐binding protein 3 mediates anti‐influenza activity... 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 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The FASEB journal Wiley

A new splice variant of the human guanylate‐binding protein 3 mediates anti‐influenza activity through inhibition of viral transcription and replication

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References (35)

Publisher
Wiley
Copyright
© Federation of American Societies for Experimental Biology
ISSN
0892-6638
eISSN
1530-6860
DOI
10.1096/fj.11-189886
Publisher site
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Abstract

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

Journal

The FASEB journal – Wiley

Published: Mar 1, 2012

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