The M33 chemokine receptor homolog of murine cytomegalovirus exhibits a differential tissue-specific role during in vivo replication and latency.

Cardin, Rhonda D., Schaefer, Gregory C., Allen, Janelle R., Davis-Poynter, Nicholas J. and Farrell, Helen E. (2009) The M33 chemokine receptor homolog of murine cytomegalovirus exhibits a differential tissue-specific role during in vivo replication and latency.. Journal of Virology, 83 15: 7590-7601. doi:10.1128/JVI.00386-09


Author Cardin, Rhonda D.
Schaefer, Gregory C.
Allen, Janelle R.
Davis-Poynter, Nicholas J.
Farrell, Helen E.
Title The M33 chemokine receptor homolog of murine cytomegalovirus exhibits a differential tissue-specific role during in vivo replication and latency.
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
Publication date 2009-08
Year available 2009
Sub-type Article (original research)
DOI 10.1128/JVI.00386-09
Open Access Status DOI
Volume 83
Issue 15
Start page 7590
End page 7601
Total pages 12
Editor Lynn W Enquist
Place of publication Washington, D.C., USA
Publisher American Society for Microbiology
Collection year 2010
Language eng
Subject 060506 Virology
0605 Microbiology
060502 Infectious Agents
920109 Infectious Diseases
920117 Skin and Related Disorders
C1
Abstract 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.
Formatted abstract
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, ΔM33BT2, 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, ΔM33BT2 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 ΔM33BT2 viral DNA levels in the latently infected spleens, lungs, and bone marrow. Following i.n. inoculation, latent ΔM33BT2 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 ΔM33BT2 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.
Keyword mouse cytomegalovirus
G protein-coupled receptor
viral latency
viral tissue tropism
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Thu, 03 Sep 2009, 07:52:57 EST by Mr Andrew Martlew on behalf of Clinical Medical Virology Centre