Chemokine binding protein M3 of murine gammaherpesvirus 68 modulates the host response to infection in a natural host

David J. Hughes, Anja Kipar, Gail H. Leeming, Elaine Bennett, Deborah Howarth, Joanne A. Cummerson, Rita Papoula-Pereira, Brian F. Flanagan, Jeffery Sample, James P. Stewart

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus). Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT) in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology.

Original languageEnglish (US)
Article numbere1001321
JournalPLoS pathogens
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2011

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Rhadinovirus
Chemokines
Carrier Proteins
Herpesviridae Infections
Infection
Lung
Spleen
Murinae
Germinal Center
Lymphoid Tissue
Bronchi
Respiratory Tract Infections
Cytokines
Viruses
Proteins

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Hughes, D. J., Kipar, A., Leeming, G. H., Bennett, E., Howarth, D., Cummerson, J. A., ... Stewart, J. P. (2011). Chemokine binding protein M3 of murine gammaherpesvirus 68 modulates the host response to infection in a natural host. PLoS pathogens, 7(3), [e1001321]. https://doi.org/10.1371/journal.ppat.1001321
Hughes, David J. ; Kipar, Anja ; Leeming, Gail H. ; Bennett, Elaine ; Howarth, Deborah ; Cummerson, Joanne A. ; Papoula-Pereira, Rita ; Flanagan, Brian F. ; Sample, Jeffery ; Stewart, James P. / Chemokine binding protein M3 of murine gammaherpesvirus 68 modulates the host response to infection in a natural host. In: PLoS pathogens. 2011 ; Vol. 7, No. 3.
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abstract = "Murine γ-herpesvirus 68 (MHV-68) infection of Mus musculus-derived strains of mice is an attractive model of γ-herpesvirus infection. Surprisingly, however, ablation of expression of MHV-68 M3, a secreted protein with broad chemokine-binding properties in vitro, has no discernable effect during experimental infection via the respiratory tract. Here we demonstrate that M3 indeed contributes significantly to MHV-68 infection, but only in the context of a natural host, the wood mouse (Apodemus sylvaticus). Specifically, M3 was essential for two features unique to the wood mouse: virus-dependent inducible bronchus-associated lymphoid tissue (iBALT) in the lung and highly organized secondary follicles in the spleen, both predominant sites of latency in these organs. Consequently, lack of M3 resulted in substantially reduced latency in the spleen and lung. In the absence of M3, splenic germinal centers appeared as previously described for MHV-68-infected laboratory strains of mice, further evidence that M3 is not fully functional in the established model host. Finally, analyses of M3's influence on chemokine and cytokine levels within the lungs of infected wood mice were consistent with the known chemokine-binding profile of M3, and revealed additional influences that provide further insight into its role in MHV-68 biology.",
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Hughes, DJ, Kipar, A, Leeming, GH, Bennett, E, Howarth, D, Cummerson, JA, Papoula-Pereira, R, Flanagan, BF, Sample, J & Stewart, JP 2011, 'Chemokine binding protein M3 of murine gammaherpesvirus 68 modulates the host response to infection in a natural host', PLoS pathogens, vol. 7, no. 3, e1001321. https://doi.org/10.1371/journal.ppat.1001321

Chemokine binding protein M3 of murine gammaherpesvirus 68 modulates the host response to infection in a natural host. / Hughes, David J.; Kipar, Anja; Leeming, Gail H.; Bennett, Elaine; Howarth, Deborah; Cummerson, Joanne A.; Papoula-Pereira, Rita; Flanagan, Brian F.; Sample, Jeffery; Stewart, James P.

In: PLoS pathogens, Vol. 7, No. 3, e1001321, 01.03.2011.

Research output: Contribution to journalArticle

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AU - Hughes, David J.

AU - Kipar, Anja

AU - Leeming, Gail H.

AU - Bennett, Elaine

AU - Howarth, Deborah

AU - Cummerson, Joanne A.

AU - Papoula-Pereira, Rita

AU - Flanagan, Brian F.

AU - Sample, Jeffery

AU - Stewart, James P.

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