• Title/Summary/Keyword: Coxsackievirus and adenovirus receptor

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Enhancement of Transduction Efficiency and Antitumor Effects of IL-12N220L-expressing Adenovirus by Co-delivery of DOTAP

  • Youn, Je-In;Jin, Hyun-Tak;Sung, Young-Chul
    • IMMUNE NETWORK
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    • v.7 no.4
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    • pp.179-185
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    • 2007
  • Background: Adenovirus (Ad) vectors have been widely used for many gene therapy applications because of their high transduction ability and broad tropism. However, their utility for cancer gene therapy is limited by their poor transduction into cancer cells lacking the primary receptor, coxsackievirus and adenovirus receptor (CAR). Methods: To achieve CAR-independent gene transfer via Ad, we pretreated Ad with 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and analyzed their transduction efficiency into cancer cells in vitro and in vivo comparing with the virus alone. Results: Treatment of DOTAP significantly increased adenoviral gene transfer in tumor cells in vitro. Moreover, DOTAP at an optimum dose $(10{\mu}g/ml)$ enhanced IL-12 transgene expression by fivefold in tumor, and twofold in serum after intratumoral injection of adenovirus expressing IL-12N220L (Ad/IL-12N220L). In addition, cotreatment of DOTAP decreased tumor growth rate in the Ad/IL-12N220L-transduced tumor model, finally leading to enhanced survival rate. Conclusion: Our results strongly suggest that DOTAP could be of great utility for improving adenovirus-mediated cancer gene therapy.

Histone deacetylase inhibitor Trichostatin A enhanced the efficiency of adenovirus mediated gene transfer into non-small cell lung cancer cells

  • Park, Mi-Sun;Kang, Ho-Il;Lim, Sin-Ae;Jee, Seung-Wan;Eom, Mi-Ok;Ryeom, Tai-Kyung;Kim, Ok-Hee
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.99.2-99.2
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    • 2003
  • One of the major limitations in using adenoviral vector for gene therapy is inefficient infection of host cells. The presence of coxsackievirus and adenovirus receptor (CAR) and ${\alpha}$-integrin on cell surfaces is required for efficient adenovirus infection. In this study, we investigated the effect of trichostatin A, a histone deacetylase inhibitor, on transfection efficiency after transduction of adenovirus mediated p16$\^$INK4a/ gene transfer. In our previous study, p16$\^$INK4a/ tumor suppressor gene transfer in the non-small cell lung cancer cells (A549 cells) by transduction of recombinant adenovirus (Ad5CMV-p16) resulted in significant inhibition of cancer cell proliferation. (omitted)

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Obesity Exacerbates Coxsackievirus Infection via Lipid-Induced Mitochondrial Reactive Oxygen Species Generation

  • Seong-Ryeol Kim;Jae-Hyoung Song;Jae-Hee Ahn;Myeong Seon Jeong;Yoon Mee Yang;Jaewon Cho;Jae-Hyeon Jeong;Younggil Cha;Kil-Nam Kim;Hong Pyo Kim;Sun-Young Chang;Hyun-Jeong Ko
    • IMMUNE NETWORK
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    • v.22 no.2
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    • pp.19.1-19.20
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    • 2022
  • Coxsackievirus B3 (CVB3) infection causes acute pancreatitis and myocarditis. However, its pathophysiological mechanism is unclear. Here, we investigated how lipid metabolism is associated with exacerbation of CVB3 pathology using high-fat diet (HFD)-induced obese mice. Mice were intraperitoneally inoculated with 1×106 pfu/mouse of CVB3 after being fed a control or HFD to induce obesity. Mice were treated with mitoquinone (MitoQ) to reduce the level of mitochondrial ROS (mtROS). In obese mice, lipotoxicity of white adipose tissue-induced inflammation caused increased replication of CVB3 and mortality. The coxsackievirus adenovirus receptor increased under obese conditions, facilitating CVB3 replication in vitro. However, lipid-treated cells with receptor-specific inhibitors did not reduce CVB3 replication. In addition, lipid treatment increased mitochondria-derived vesicle formation and the number of multivesicular bodies. Alternatively, we found that inhibition of lipid-induced mtROS decreased viral replication. Notably, HFD-fed mice were more susceptible to CVB3-induced mortality in association with increased levels of CVB3 replication in adipose tissue, which was ameliorated by administration of the mtROS inhibitor, MitoQ. These results suggest that mtROS inhibitors can be used as potential treatments for CVB3 infection.

Efficient Transduction with Recombinant Adenovirus in EBV-transformed B Lymphoblastoid Cell Lines

  • Kim, Hye-Jin;Cho, Hyun-Il;Han, Yoon-Hee;Park, Soo-Young;Kim, Dong-Wook;Lee, Dong-Gun;Kim, Jee-Hoon;Shin, Wan-Shik;Paik, Soon-Young;Kim, Chun-Choo;Hong, Young-Seon;Kim, Tai-Gyu
    • BMB Reports
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    • v.37 no.3
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    • pp.376-382
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    • 2004
  • The Epstein-Barr-transformed B lymphoblastoid cell lines, LCL, which express antigens, are potential antigen-presenting cells (APCs) for the induction of cytotoxic T lymphocytes in vitro. However, transfecting LCL with subsequent selection by antibiotics is notoriously difficult because the plating efficiencies of LCL are reported to be 1% or less. Therefore, this study investigated the optimal conditions for increasing the transduction efficiency of a recombinant adenovirus to LCL for use as a source of APCs. The transduction efficiencies were < 13% (SD $\pm$ 2.13) at a multiplicity of infection (MOI) of 100, while it was increased to 28% (SD $\pm$ 9.43) at an MOI of 1000. Moreover, its efficiencies to LCL that expressed the coxsackie adenovirus receptor were increased to 60% (SD $\pm$ 6.35) at an MOI of 1000, and were further increased to 70% (SD $\pm$ 4.56) when combined with the centrifugal method. The cationic liposome or anionic polymer had no effect on the transduction efficiency when compared to that of the centrifugal method. These results may be used as a convenient source of target cells for a CTL assay and/or autologous APCs for the induction of the in vitro CTL responses that are specific to viral and tumor antigens.

Tight Junction Assembly Ensures Maintenance of Pregnancy during Embryogenesis in a Mouse Model

  • Jeong, Yelin;Choi, Inchul
    • Journal of Animal Reproduction and Biotechnology
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    • v.34 no.4
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    • pp.318-321
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    • 2019
  • Recent studies showed that tight junctions (TJs) integrity and assembly are required for blastocyst development in mouse and pig models. However, the biological functions of TJs associated with embryo implantation and maintenance of pregnancy were not investigated yet. To examine whether disrupted TJs affect further embryo development, we employed RNAi approach and inhibitor treatment. The embryos were injected with Cxadr (Coxsackievirus and adenovirus receptor) siRNA for knock down (KD) and treated with Adam10 (A Disintegrin and Metalloproteinase specific inhibitor 10; GI254023X; SI). We compared blastocyst development and paracellular sealing assay using FITC dextran uptake between control and KD or SI embryos. Finally, we transferred control and Cxadr KD or Adam 10 SI treated blastocyst to uteri of recipients. Cxadr KD and Adam 10 SI showed lower blastocyst development and more permeable to FITC-dextran. Moreover, we observed that half of KD and inhibited embryos failed to maintain pregnancies after the second trimester. Our findings suggested that TJs integrity is required for the maintenance of pregnancy and can be used as a selective marker for the successful application of assisted reproduction technologies.