@article{WeibelRaabYuetal.2011,
  author    = {Weibel, Stephanie and Raab, Viktoria and Yu, Yong A. and Worschech, Andrea and Wang, Ena and Marincola, Francesco M. and Szalay, Aladar A.},
  title     = {Viral-mediated oncolysis is the most critical factor in the late-phase of the tumor regression process upon vaccinia virus infection},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68691},
  year      = {2011},
  abstract  = {Background: In principle, the elimination of malignancies by oncolytic virotherapy could proceed by different mechanisms - e.g. tumor cell specific oncolysis, destruction of the tumor vasculature or an anti-tumoral immunological response. In this study, we analyzed the contribution of these factors to elucidate the responsible mechanism for regression of human breast tumor xenografts upon colonization with an attenuated vaccinia virus (VACV). Methods: Breast tumor xenografts were analyzed 6 weeks post VACV infection (p.i.; regression phase) by immunohistochemistry and mouse-specific expression arrays. Viral-mediated oncolysis was determined by tumor growth analysis combined with microscopic studies of intratumoral virus distribution. The tumor vasculature was morphologically characterized by diameter and density measurements and vessel functionality was analyzed by lectin perfusion and extravasation studies. Immunological aspects of viral-mediated tumor regression were studied in either immune-deficient mouse strains (T-, B-, NK-cell-deficient) or upon cyclophosphamide-induced immunosuppression (MHCII+-cell depletion) in nude mice. Results: Late stage VACV-infected breast tumors showed extensive necrosis, which was highly specific to cancer cells. The tumor vasculature in infected tumor areas remained functional and the endothelial cells were not infected. However, viral colonization triggers hyperpermeability and dilatation of the tumor vessels, which resembled the activated endothelium in wounded tissue. Moreover, we demonstrated an increased expression of genes involved in leukocyte-endothelial cell interaction in VACV-infected tumors, which orchestrate perivascular inflammatory cell infiltration. The immunohistochemical analysis of infected tumors displayed intense infiltration of MHCII-positive cells and colocalization of tumor vessels with MHCII+/CD31+ vascular leukocytes. However, GI-101A tumor growth analysis upon VACV-infection in either immunosuppressed nude mice (MHCII+-cell depleted) or in immune-deficient mouse strains (T-, B-, NK-cell-deficient) revealed that neither MHCII-positive immune cells nor T-, B-, or NK cells contributed significantly to VACV-mediated tumor regression. In contrast, tumors of immunosuppressed mice showed enhanced viral spreading and tumor necrosis. Conclusions: Taken together, these results indicate that VACV-mediated oncolysis is the primary mechanism of tumor shrinkage in the late regression phase. Neither the destruction of the tumor vasculature nor the massive VACV-mediated intratumoral inflammation was a prerequisite for tumor regression. We propose that approaches to enhance viral replication and spread within the tumor microenvironment should improve therapeutical outcome.},
  subject      = {Virusinfektion},
  language  = {en}
}
@phdthesis{Proettel2011,
  author    = {Pr{\"o}ttel, Anika},
  title     = {Nachweis humaner WU-Polyomavirus-DNA mittels real-time Polymerase Kettenreaktion in Nasenrachensekreten, Serum- und Stuhlproben von Kindern mit akuten respiratorischen Erkrankungen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-71187},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Das humanes WU Polyomavirus wurde im Jahr 2007 als ein neues Virus in Proben des Respirationstraktes beschrieben und geh{\"o}rt zur Familie der Polpymaviridae. Das Ziel der Arbeit war es, eine WUPyV-rea-time-PCR zu etablieren und zu evaluieren und mit dieser neuen Methode WUPyV-DNA in Nasenrachenskreten (NRS) zu detektieren und zu quantifizieren. Insgesamt wurden 1232 NRS von Patientin mit akuten respiratoischen Erkrankungen, die an der Universit{\"a}tskinderklinik W{\"u}rzburg im Zeitraum von Januar 2002 bis September 2005 und Januar 2007 bis July 2007 station{\"a}r behandelt worden waren, auf WUPyV-DNA getestet. Zus{\"a}tzlich wurden 14 Serum- und 14 Stuhlproben von Kindern mit WUPyV-DNA-pos. NRS getestet. Mit der real-time PCR wurde WUPyV-DNA in 5,2 \% der 1232 NRS detektiert. Der Viruslastmedian aller WUPyV-positiven NRS betrug 950 Kopien/m. Neben einigen sehr hohen Viruslasten (4,7 \% > E9 Kopien/ml) wurden vor allem niedirge Viruslaten (51,6 \% < 1000 Kopien/ml) mit der WUPyV-real-time PCR nachgewiesen. Es ergaben sich keine statistisch signifikanten Zusammenh{\"a}nge zwischen der Viruslast und der Koinfektionen mit anderen respiratorischen Viren, mit klinischer Diagnose, mit dem Alter der infizierten Kinder und mit dem jahreszeitlichen Auftreten. In 3 der 14 Serum und 2 der 14 Stuhlproben konnte WUPyV-DNA detektiert werden. Vir{\"a}mische Kinder hatten tendenzen zu h{\"o}hrer Viruslast im NRS.Weitere Studien sind notwendig um die pathogenetische Relevanz des WUPyV f{\"u}r den Menschen zu untersuchen. Die in dieser Arbeit etablierte real-time PCR zur WUPyV-Quantifizierung kann dabei zur Anwendung kommen.},
  subject      = {JC-Virus},
  language  = {de}
}