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

作者：Frederico Bruno; Chao Brittany; May Janet S; Belz Gabrielle T; Stevenson Philip G^*

来源：Cell Host & Microbe, 2014, 15(4): 457-470.

DOI：10.1016/j.chom.2014.03.010

Gamma-herpesviruses (gamma HVs) 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 gamma HV, exploits normal immune communication routes to spread by serial lymphoid/myeloid exchange.

• 出版日期2014-4-9
• 单位河北医科大学