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Journal of Virology, March 2008, p. 2208-2217, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01718-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Repetitive Region of Gammaherpesvirus Genomic DNA Is a Ligand for Induction of Type I Interferon{triangledown}

David Jesse Sanchez,1 Daniel Miranda Jr.,1 Vaithilingaraja Arumugaswami,2 Seungmin Hwang,2 Adam E. Singer,3 Ashkon Senaati,1 Arash Shahangian,1,4 Moon Jung Song,5 Ren Sun,2,6,7 and Genhong Cheng1,6*

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California,1 Department of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, California,2 Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, California,3 MSTP Graduate Program, University of California, Los Angeles, Los Angeles, California,4 Division of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea,5 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, California,6 UCLA AIDS Institute, University of California, Los Angeles, Los Angeles, California7

Received 7 August 2007/ Accepted 4 December 2007

Innate immune responses against viral infection, especially the induction of type I interferon, are critical for limiting the replication of the virus. Although it has been shown that DNA can induce type I interferon, to date no natural DNA ligand of a virus that induces type I interferon has been described. Here we screened the genome of murine gammaherpesvirus 68 with mutations at various genomic locations to map the region of DNA that induces type I interferon. A repetitive region termed the 100-base-pair repeat region is a ligand that is both necessary and sufficient for the viral genomic DNA to induce type I interferon. A region colinear with this ligand in the genome of Kaposi's sarcoma-associated herpesvirus also induces type I interferon. We have thus defined a repetitive region of the genomes of gammaherpesviruses as the first natural DNA virus ligand that induces type I interferon.


* Corresponding author. Mailing address: Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095. Phone: (310) 825-8896. Fax: (310) 206-5231. E-mail: gcheng{at}mednet.ucla.edu

{triangledown} Published ahead of print on 12 December 2007.


Journal of Virology, March 2008, p. 2208-2217, Vol. 82, No. 5
0022-538X/08/$08.00+0     doi:10.1128/JVI.01718-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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