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Journal of Virology, August 2009, p. 7590-7601, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00386-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The M33 Chemokine Receptor Homolog of Murine Cytomegalovirus Exhibits a Differential Tissue-Specific Role during In Vivo Replication and Latency{triangledown}

Rhonda D. Cardin,1* Gregory C. Schaefer,1 Janelle R. Allen,1 Nicholas J. Davis-Poynter,2 and Helen E. Farrell2

Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio,1 Sir Albert Sakzewski Virus Research Center, Royal Children's Hospital, and Clinical Medical Virology Center, University of Queensland, Brisbane, Australia2

Received 20 February 2009/ Accepted 6 May 2009

M33, encoded by murine cytomegalovirus (MCMV), is a member of the UL33 homolog G-protein-coupled receptor (GPCR) family and is conserved across all the betaherpesviruses. Infection of mice with recombinant viruses lacking M33 or containing specific signaling domain mutations in M33 results in significantly diminished MCMV infection of the salivary glands. To determine the role of M33 in viral dissemination and/or infection in other tissues, viral infection with wild-type K181 virus and an M33 mutant virus, {Delta}M33BT2, was characterized using two different routes of inoculation. Following both intraperitoneal (i.p.) and intranasal (i.n.) inoculation, M33 was attenuated for infection of the spleen and pancreas as early as 7 days after infection. Following i.p. inoculation, {Delta}M33BT2 exhibited a severe defect in latency as measured by a diminished capacity to reactivate from spleens and lungs in reactivation assays (P < 0.001). Subsequent PCR analysis revealed markedly reduced {Delta}M33BT2 viral DNA levels in the latently infected spleens, lungs, and bone marrow. Following i.n. inoculation, latent {Delta}M33BT2 viral DNA was significantly reduced in the spleen and, in agreement with results from i.p. inoculation, did not reactivate from the spleen (P < 0.001). Furthermore, in vivo complementation of {Delta}M33BT2 virus replication and/or dissemination to the salivary glands and pancreas was achieved by coinfection with wild-type virus. Overall, our data suggest a critical tissue-specific role for M33 during infection in the salivary glands, spleen, and pancreas but not the lungs. Our data suggest that M33 contributes to the efficient establishment or maintenance of long-term latent MCMV infection.

* Corresponding author. Mailing address: Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229. Phone: (513) 636-2420. Fax: (513) 636-7655. E-mail: rhonda.cardin{at}cchmc.org

{triangledown} Published ahead of print on 13 May 2009.

Journal of Virology, August 2009, p. 7590-7601, Vol. 83, No. 15
0022-538X/09/$08.00+0     doi:10.1128/JVI.00386-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sherrill, J. D., Stropes, M. P., Schneider, O. D., Koch, D. E., Bittencourt, F. M., Miller, J. L. C., Miller, W. E. (2009). Activation of Intracellular Signaling Pathways by the Murine Cytomegalovirus G Protein-Coupled Receptor M33 Occurs via PLC-{beta}/PKC-Dependent and -Independent Mechanisms. J. Virol. 83: 8141-8152 [Abstract] [Full Text]  


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