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Journal of Virology, September 2008, p. 8500-8508, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00186-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Replication-Defective Gammaherpesvirus Efficiently Establishes Long-Term Latency in Macrophages but Not in B Cells In Vivo {triangledown}

Haiyan Li, Kazufumi Ikuta, John W. Sixbey, and Scott A. Tibbetts*

Center for Molecular and Tumor Virology, Department of Microbiology and Immunology, Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130

Received 25 January 2008/ Accepted 9 June 2008

Murine gammaherpesvirus 68 ({gamma}HV68 or MHV68) is genetically related to the human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), providing a useful system for in vivo studies of the virus-host relationship. To begin to address fundamental questions about the mechanisms of the establishment of gammaherpesvirus latency, we previously generated a replication-defective {gamma}HV68 lacking the expression of the single-stranded DNA binding protein encoded by orf6. In work presented here, we demonstrate that this mutant virus established a long-term infection in vivo that was molecularly identical to wild-type virus latency. Thus, despite the absence of an acute phase of lytic replication, the mutant virus established a chronic infection in which the viral genome (i) was maintained as an episome and (ii) expressed latency-associated, but not lytic replication-associated, genes. Macrophages purified from mice infected with the replication-defective virus harbored viral genome at a frequency that was nearly identical to that of wild-type {gamma}HV68; however, the frequency of B cells harboring viral genome was greatly reduced in the absence of lytic replication. Thus, this replication-defective gammaherpesvirus efficiently established in vivo infection in macrophages that was molecularly indistinguishable from wild-type virus latency. These data point to a critical role for lytic replication or reactivation in the establishment or maintenance of latent infection in B cells.

* Corresponding author. Mailing address: Center for Molecular and Tumor Virology, Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130. Phone: (318) 675-8148. Fax: (318) 675-5764. E-mail: stibbe{at}lsuhsc.edu

{triangledown} Published ahead of print on 18 June 2008.

Journal of Virology, September 2008, p. 8500-8508, Vol. 82, No. 17
0022-538X/08/$08.00+0     doi:10.1128/JVI.00186-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Siegel, A. M., Rangaswamy, U. S., Napier, R. J., Speck, S. H. (2010). Blimp-1-Dependent Plasma Cell Differentiation Is Required for Efficient Maintenance of Murine Gammaherpesvirus Latency and Antiviral Antibody Responses. J. Virol. 84: 674-685 [Abstract] [Full Text]  


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