This Article Full Text Full Text (PDF) Supplemental material Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zahn, R. C. Articles by von Laer, D. Search for Related Content PubMed PubMed Citation Articles by Zahn, R. C. Articles by von Laer, D.

 Previous Article  |  Next Article 

Journal of Virology, January 2007, p. 457-464, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.00067-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

A-to-G Hypermutation in the Genome of Lymphocytic Choriomeningitis Virus ^,

Roland C. Zahn,¹ Ina Schelp,¹ Olaf Utermöhlen,² and Dorothee von Laer^1*

Georg-Speyer-Haus, Institute for Biomedical Research, 60596 Frankfurt am Main, Germany,¹ Institute for Medical Microbiology, Immunology and Hygiene, Medical Center of the University of Cologne, 50935 Cologne, Germany²

Received 10 January 2006/ Accepted 8 May 2006

The interferon-inducible adenosine deaminase that acts on double-stranded RNA (ADAR1-L) has been proposed to be one of the antiviral effector proteins within the complex innate immune response. Here, the potential role of ADAR1-L in the innate immune response to lymphocytic choriomeningitis virus (LCMV), a widely used virus model, was studied. Infection with LCMV clearly upregulated ADAR1-L expression and activity. The editing activity of ADAR1-L on an RNA substrate was not inhibited by LCMV replication. Accordingly, an adenosine-to-guanosine (A-to-G) and uracil-to-cytidine (U-to-C) hypermutation pattern was found in the LCMV genomic RNA in infected cell lines and in mice. In addition, two hypermutated clones with a high level of A-to-G or U-to-C mutations within a short stretch of the viral genome were isolated. Analysis of the functionality of viral glycoprotein revealed that A-to-G- and U-to-C-mutated LCMV genomes coded for nonfunctional glycoprotein at a surprisingly high frequency. Approximately half the GP clones with an amino acid mutation lacked functionality. These results suggest that ADAR1-L-induced mutations in the viral RNA lead to a loss of viral protein function and reduced viral infectivity. This study therefore provides strong support for the contribution of ADAR1-L to the innate antiviral immune response.

---

* Corresponding author. Mailing address: Georg-Speyer-Haus, Paul-Ehrlich-Str. 42-44, 60596 Frankfurt, Germany, Phone: 49 69 63395 232. Fax: 49 69 63395 297. E-mail: laer{at}em.uni-frankfurt.de.

Published ahead of print on 4 October 2006.

Supplemental material for this article may be found at http://jvi.asm.org/.

---

Journal of Virology, January 2007, p. 457-464, Vol. 81, No. 2
0022-538X/07/$08.00+0     doi:10.1128/JVI.00067-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Toth, A. M., Li, Z., Cattaneo, R., Samuel, C. E. (2009). RNA-specific Adenosine Deaminase ADAR1 Suppresses Measles Virus-induced Apoptosis and Activation of Protein Kinase PKR. J. Biol. Chem. 284: 29350-29356 [Abstract] [Full Text]  
• Doria, M., Neri, F., Gallo, A., Farace, M. G., Michienzi, A. (2009). Editing of HIV-1 RNA by the double-stranded RNA deaminase ADAR1 stimulates viral infection. Nucleic Acids Res 37: 5848-5858 [Abstract] [Full Text]  
• Randall, R. E., Goodbourn, S. (2008). Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J. Gen. Virol. 89: 1-47 [Abstract] [Full Text]