1887

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 (HV-68) could infect immature or mature bone-marrow-derived DCs and what effect infection had on DC maturation. It was found that 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 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 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 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, 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 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 HV-68 infection blocked maturation. Taken together, these data demonstrate that 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 HV-68.

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2007-07-01
2019-11-15
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