Chemokine Binding Protein M3 of Murine Gammaherpesvirus 68 Modulates the Host Response to Infection in a Natural Host

Hughes, David J, Kipar, Anja ORCID: 0000-0001-7289-3459, Leeming, Gail H ORCID: 0000-0003-3409-399X, Bennett, Elaine, Howarth, Deborah, Cummerson, Joanne A, Papoula-Pereira, Rita, Flanagan, Brian F, Sample, Jeffery T and Stewart, James P ORCID: 0000-0002-8928-2037 (2011) Chemokine Binding Protein M3 of Murine Gammaherpesvirus 68 Modulates the Host Response to Infection in a Natural Host. PLOS PATHOGENS, 7 (3). e1001321-. ISSN 1553-7366, 1553-7374

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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.

Item Type:	Article
Additional Information:	## TULIP Type: Articles/Papers (Journal) ##
Uncontrolled Keywords:	Lung, Bronchi, Lymphoid Tissue, Spleen, Cell Line, Animals, Mice, Gammaherpesvirinae, Herpesviridae Infections, Viral Proteins, Chemokines, Virus Latency, Cricetinae, Murinae
Depositing User:	Symplectic Admin
Date Deposited:	23 Mar 2015 12:04
Last Modified:	07 Dec 2024 15:10
DOI:	10.1371/journal.ppat.1001321
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/2007322