Journal article

A Murid Gamma-Herpesviruses Exploits Normal Splenic Immune Communication Routes for Systemic Spread

Bruno Frederico, Brittany Chao, Janet S May, Gabrielle T Belz, Philip G Stevenson

Cell Host & Microbe | CELL PRESS | Published : 2014

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..

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University of Melbourne Researchers

Grants

Awarded by ARC


Awarded by BBSRC


Awarded by NHMRC


Awarded by Biotechnology and Biological Sciences Research Council


Funding Acknowledgements

B.F. is supported by the Portuguese Foundation for Science and Technology, and B. C. by the Gates Foundation. This work was also supported by grants from the ARC (FT130100138), BBSRC (BB/J014419/1), NHMRC (637319, 1060138, 1064015), and Belspo (BelVir).