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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{triangledown} ,{dagger}

Roland C. Zahn,1 Ina Schelp,1 Olaf Utermöhlen,2 and Dorothee von Laer1*

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.

{triangledown} Published ahead of print on 4 October 2006.

{dagger} 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:

  • 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]  


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