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Cell Host Microbe. 2014 Apr 9;15(4):457-70. doi: 10.1016/j.chom.2014.03.010.

A murid gamma-herpesviruses exploits normal splenic immune communication routes for systemic spread.

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Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 2QQ, UK.
Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia.
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 2QQ, UK; Sir Albert Sakzewski Virus Research Centre and Queensland Children's Medical Research Institute, University of Queensland, Brisbane, Queensland 4029, Australia. Electronic address:


Gamma-herpesviruses (γHVs) are widespread oncogenic pathogens that chronically infect circulating lymphocytes. How they subvert the immune check-point function of the spleen to promote persistent infection is not clear. We show that Murid Herpesvirus-4 (MuHV-4) enters the spleen by infecting marginal zone (MZ) macrophages, which provided a conduit to MZ B cells. Relocation of MZ B cells to the white pulp allowed virus transfer to follicular dendritic cells. From here the virus reached germinal center B cells to establish persistent infection. Mice lacking MZ B cells, or treated with a sphingosine-1-phosphate receptor agonist to dislocate them, were protected against MuHV-4 colonization. MuHV-4 lacking ORF27, which encodes a glycoprotein necessary for efficient intercellular spread, could infect MZ macrophages but was impaired in long-term infection. Thus, MuHV-4, a γHV, exploits normal immune communication routes to spread by serial lymphoid/myeloid exchange.

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