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*
Laboratory of Cellular Oncology, National Cancer Institute, and
Laboratory of Molecular Medicine and Neuroscience, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892
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-
; 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-
. 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.
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J. C. Steele, S. Roberts, S. M. Rookes, and P. H. Gallimore Detection of CD4+- and CD8+-T-Cell Responses to Human Papillomavirus Type 1 Antigens Expressed at Various Stages of the Virus Life Cycle by Using an Enzyme-Linked Immunospot Assay of Gamma Interferon Release J. Virol., May 13, 2002; 76(12): 6027 - 6036. [Abstract] [Full Text] [PDF]
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T. Storni, F. Lechner, I. Erdmann, T. Bachi, A. Jegerlehner, T. Dumrese, T. M. Kundig, C. Ruedl, and M. F. Bachmann Critical Role for Activation of Antigen-Presenting Cells in Priming of Cytotoxic T Cell Responses After Vaccination with Virus-Like Particles J. Immunol., March 15, 2002; 168(6): 2880 - 2886. [Abstract] [Full Text] [PDF]
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A. Touze, L. Bousarghin, C. Ster, A.-L. Combita, P. Roingeard, and P. Coursaget Gene transfer using human polyomavirus BK virus-like particles expressed in insect cells J. Gen. Virol., December 1, 2001; 82(12): 3005 - 3009. [Abstract] [Full Text] [PDF]
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B. Clark, W. Caparros-Wanderley, G. Musselwhite, M. Kotecha, and B. E. Griffin Immunity against both polyomavirus VP1 and a transgene product induced following intranasal delivery of VP1 pseudocapsid-DNA complexes J. Gen. Virol., November 1, 2001; 82(11): 2791 - 2797. [Abstract] [Full Text] [PDF]
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W. Shi, J. Liu, Y. Huang, and L. Qiao Papillomavirus Pseudovirus: a Novel Vaccine To Induce Mucosal and Systemic Cytotoxic T-Lymphocyte Responses J. Virol., November 1, 2001; 75(21): 10139 - 10148. [Abstract] [Full Text] [PDF]
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