title: Papillomavirus-like particles induce acute activation of dendritic cells.
abstract: The role of viral structural proteins in the initiation of adaptive immune responses is poorly understood. To address this issue, we focused on the effect of noninfectious papillomavirus-like particles (VLPs) on dendritic cell (DC) activation. We found that murine bone marrow-derived dendritic cells (BMDCs) effectively bound and rapidly internalized bovine papillomavirus VLPS: Exposure to fully assembled VLPs of bovine papillomavirus, human papillomavirus (HPV)16 or HPV18, but not to predominately disordered HPV16 capsomers, induced acute phenotypic maturation of BMDCS: Structurally similar polyomavirus VLPs bound to the DC surface and were internalized, but failed to induce maturation. DCs that had incorporated HPV16 VLPs produced proinflammatory cytokines IL-6 and TNF-alpha; however, the release of these cytokines was delayed relative to LPS activation. Production of IL-12p70 by VLP-exposed DCs required the addition of syngeneic T cells or rIFN-gamma. Finally, BMDCs pulsed with HPV16 VLPs induced Th1-dominated primary T cell responses in vitro. Our data provide evidence that DCs respond to intact papillomavirus capsids and that they play a central role in VLP-induced immunity. These results offer a mechanistic explanation for the striking ability of papillomavirus VLP-based vaccines to induce potent T and B cell responses even in the absence of adjuvant.
authors: Laboratory of Cellular Oncology, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
authors: P
authors: P
authors: Lenz
authors: P M
authors: PM
authors: Day
authors: Y Y
authors: YY
authors: Pang
authors: S A
authors: SA
authors: Frye
authors: P N
authors: PN
authors: Jensen
authors: D R
authors: DR
authors: Lowy
authors: J T
authors: JT
authors: Schiller
mesh_terms: D000818:Animals; D001739:BK Virus / Q000276:immunology; D052688:Bovine papillomavirus 1 / Q000276:immunology*; D002213:Capsid / Q000276:immunology / Q000378:metabolism; D036022:Capsid Proteins; D002417:Cattle; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D006801:Humans; D016130:Immunophenotyping; D018836:Inflammation Mediators / Q000378:metabolism; D007399:Interphase / Q000276:immunology; D007577:JC Virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D027383:Papillomaviridae / Q000235:genetics / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000821:virology; D014771:Virion / Q000276:immunology*; D019065:Virus Assembly / Q000235:genetics / Q000276:immunology
chemical_list: D036022:Capsid Proteins; D016207:Cytokines; D018836:Inflammation Mediators; C085217:L1 protein, Bovine papillomavirus; C085218:L2 protein, Bovine papillomavirus; D009856:Oncogene Proteins, Viral; C063317:L1 protein, Human papillomavirus type 16