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

Abstract

Many viruses have evolved mechanisms to evade host immunity by subverting the function of dendritic cells (DCs). This study determined whether murine gammaherpesvirus-68 (gamma HV-68) could infect immature or mature bone-marrow-derived DCs and what effect infection had on DC maturation. It was found that gamma HV-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 with gamma HV-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 with gamma HV-68. Electron microscopy revealed the presence of capsids in the nucleus of immature DCs but not in mature DCs. Interestingly, infection of immature DCs by gamma HV-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, gamma HV-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 of gamma HV-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 that gamma HV-68 infection blocked maturation. Taken together, these data demonstrate that gamma HV-68 infection of DCs differs depending on the maturation state of the DC. Moreover, the block in DC maturation suggests a possible immunoevasion strategy by gamma HV-68.