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Browsing by Subject "Dependovirus"
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Item AAV and hepatitis: Cause or coincidence?(Elsevier, 2022) de Jong, Ype P.; Herzog, Roland W.; Pediatrics, School of MedicineItem AAV Immunogenicity: New Answers Create New Questions(Elsevier, 2018-11-07) Shirley, Jamie L.; Herzog, Roland W.; Pediatrics, School of MedicineComment on Exposure to wild-type AAV drives distinct capsid immunity profiles in humans. [J Clin Invest. 2018]Item AAV Joins the Rank of Genotoxic Vectors(Cell Press, 2021) Davé, Utpal P.; Cornetta, Kenneth; Medicine, School of MedicineItem "D" matters in recombinant AAV DNA packaging(Elsevier, 2021) Zhang, Junping; Guo, Ping; Xu, Yinxia; Mulcrone, Patrick L.; Samulski, R. Jude; Xiao, Weidong; Pediatrics, School of MedicineItem Encouraging and Unsettling Findings in Long-Term Follow-up of AAV Gene Transfer(Elsevier, 2020-02-05) Herzog, Roland W.; Pediatrics, School of MedicineItem Flies in the ointment: AAV vector preparations and tumor risk(Elsevier, 2021) Zhang, Junping; Yu, Xiangping; Herzog, Roland W.; Samulski, R. Jude; Xiao, Weidong; Pediatrics, School of MedicineItem Genetic ablation of Cullin-RING E3 ubiquitin ligase 7 restrains pressure overload-induced myocardial fibrosis(PLOS, 2020-12-22) Anger, Melanie; Scheufele, Florian; Ramanujam, Deepak; Meyer, Kathleen; Nakajima, Hidehiro; Field, Loren J.; Engelhardt, Stefan; Sarikas, Antonio; Medicine, School of MedicineFibrosis is a pathognomonic feature of structural heart disease and counteracted by distinct cardioprotective mechanisms, e.g. activation of the phosphoinositide 3-kinase (PI3K) / AKT pro-survival pathway. The Cullin-RING E3 ubiquitin ligase 7 (CRL7) was identified as negative regulator of PI3K/AKT signalling in skeletal muscle, but its role in the heart remains to be elucidated. Here, we sought to determine whether CRL7 modulates to cardiac fibrosis following pressure overload and dissect its underlying mechanisms. For inactivation of CRL7, the Cullin 7 (Cul7) gene was deleted in cardiac myocytes (CM) by injection of adeno-associated virus subtype 9 (AAV9) vectors encoding codon improved Cre-recombinase (AAV9-CMV-iCre) in Cul7flox/flox mice. In addition, Myosin Heavy Chain 6 (Myh6; alpha-MHC)-MerCreMer transgenic mice with tamoxifen-induced CM-specific expression of iCre were used as alternate model. After transverse aortic constriction (TAC), causing chronic pressure overload and fibrosis, AAV9-CMV-iCre induced Cul7-/- mice displayed a ~50% reduction of interstitial cardiac fibrosis when compared to Cul7+/+ animals (6.7% vs. 3.4%, p<0.01). Similar results were obtained with Cul7flox/flox Myh6-Mer-Cre-MerTg(1/0) mice which displayed a ~30% reduction of cardiac fibrosis after TAC when compared to Cul7+/+ Myh6-Mer-Cre-MerTg(1/0) controls after TAC surgery (12.4% vs. 8.7%, p<0.05). No hemodynamic alterations were observed. AKTSer473 phosphorylation was increased 3-fold (p<0.01) in Cul7-/- vs. control mice, together with a ~78% (p<0.001) reduction of TUNEL-positive apoptotic cells three weeks after TAC. In addition, CM-specific expression of a dominant-negative CUL71152stop mutant resulted in a 16.3-fold decrease (p<0.001) of in situ end-labelling (ISEL) positive apoptotic cells. Collectively, our data demonstrate that CM-specific ablation of Cul7 restrains myocardial fibrosis and apoptosis upon pressure overload, and introduce CRL7 as a potential target for anti-fibrotic therapeutic strategies of the heart.Item Intraceullar trafficking of the adeno-associated virus 2(2001) Hansen, Jonathan JamesItem Lovastatin enhances adenovirus-mediated TRAIL induced apoptosis by depleting cholesterol of lipid rafts and affecting CAR and death receptor expression of prostate cancer cells(Impact Journals, LLC, 2015-02-20) Liu, Youhong; Chen, Lin; Gong, Zhicheng; Shen, Liangfang; Kao, Chinghai; Hock, Janet M.; Sun, Lunquan; Li, Xiong; Department of Urology, IU school of MedicineOncolytic adenovirus and apoptosis inducer TRAIL are promising cancer therapies. Their antitumor efficacy, when used as single agents, is limited. Oncolytic adenoviruses have low infection activity, and cancer cells develop resistance to TRAIL-induced apoptosis. Here, we explored combining prostate-restricted replication competent adenovirus-mediated TRAIL (PRRA-TRAIL) with lovastatin, a commonly used cholesterol-lowering drug, as a potential therapy for advanced prostate cancer (PCa). Lovastatin significantly enhanced the efficacy of PRRA-TRAIL by promoting the in vivo tumor suppression, and the in vitro cell killing and apoptosis induction, via integration of multiple molecular mechanisms. Lovastatin enhanced PRRA replication and virus-delivered transgene expression by increasing the expression levels of CAR and integrins, which are critical for adenovirus 5 binding and internalization. Lovastatin enhanced TRAIL-induced apoptosis by increasing death receptor DR4 expression. These multiple effects of lovastatin on CAR, integrins and DR4 expression were closely associated with cholesterol-depletion in lipid rafts. These studies, for the first time, show correlations between cholesterol/lipid rafts, oncolytic adenovirus infection efficiency and the antitumor efficacy of TRAIL at the cellular level. This work enhances our understanding of the molecular mechanisms that support use of lovastatin, in combination with PRRA-TRAIL, as a candidate strategy to treat human refractory prostate cancer in the future.Item Mechanism of growth inhibition of primary human cells by adeno-associated virus type 2(1997) Kube, Dagmar Marie