title: 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.
authors.affiliation: Department of Microbiology and Immunology, SUNY Upstate Medical University, 750 East Adams Sweet, Syracuse, NY, USA.
authors.forename: Romana
authors.initials: R
authors.lastname: Hochreiter
authors.affiliation: Department of Microbiology and Immunology, SUNY Upstate Medical University, 750 East Adams Sweet, Syracuse, NY, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ptaschinski
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Kunkel
authors.affiliation: Department of Microbiology and Immunology, SUNY Upstate Medical University, 750 East Adams Sweet, Syracuse, NY, USA.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Rochford
mesh_terms: D000818:Animals; D016645:Aotidae; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002633:Chemotaxis; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology / Q000821:virology*; D006566:Herpesviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D041681:NIH 3T3 Cells; D011070:Poly I-C / Q000494:pharmacology; D018144:Rhadinovirus / Q000276:immunology / Q000472:pathogenicity*; D014412:Tumor Virus Infections / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12; D011070:Poly I-C