Murine gammaherpesvirus-68 productively infects immature dendritic cells and blocks maturation

Many viruses have evolved mechanisms to evade host immunity by subverting the function of dendritic cells (DCs). This study determined whether murine gammaherpesvirus-68 (γHV-68) could infect immature or mature bone-marrow-derived DCs and what effect infection had on DC maturation. It was found thatγHV-68 productively infected immature DCs, as evidenced by increased viral titres over time. If DCs were induced to mature by exposure to LPS and then infected withγHV-68, only a small percentage of cells was productively infected. However, limiting-dilution assays to measure viral reactivation demonstrated that the mature DCs were latently infected withγHV-68. Electron microscopy revealed the presence of capsids in the nucleus of immature DCs but not in mature DCs. Interestingly, infection of immature DCs byγHV-68 did not result in upregulation of the co-stimulatory molecules CD80 and CD86 or MHC class I and II, or induce cell migration, suggesting that the virus infection did not induce DC maturation. Furthermore,γHV-68 infection of immature DCs did not result in elevated interleukin-12, an important cytokine in the induction of T-cell responses. Finally, lipopolysaccharide and poly(I : C) stimulation ofγHV-68-infected immature DCs did not induce increases in the expression of co-stimulatory molecules and MHC class I or II compared with mock-treated cells, suggesting thatγHV-68 infection blocked maturation. Taken together, these data demonstrate thatγHV-68 infection of DCs differs depending on the maturation state of the DC. Moreover, the block in DC maturation suggests a possible immunoevasion strategy byγHV-68.