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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.

Author information

1
Division of Virology, Department of Pathology, University of Cambridge, Cambridge CB2 2QQ, UK.
2
Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia.
3
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: p.stevenson@uq.edu.au.

Abstract

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.

PMID:
24721574
DOI:
10.1016/j.chom.2014.03.010
[Indexed for MEDLINE]
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