國家衛生研究院 NHRI:Item 3990099045/11624
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    题名: Interference of DNAJB6/MRJ isoform switch by morpholino inhibits replication of HIV-1 and RSV
    作者: Ko, SH;Liau, YJ;Chi, YH;Lai, MJ;Chiang, YP;Lu, CY;Chang, LY;Tarn, WY;Huang, LM
    贡献者: Institute of Biotechnology and Pharmaceutical Research
    摘要: The molecular chaperon MRJ (DNAJB6) exhibits two splice isoforms that have different roles in human viral infection, but the regulatory mechanism of MRJ isoform expression is yet unclear. In this study, we show that reduction of the polyadenylation factor CstF64 was correlated with the increase of the MRJ large isoform (MRJ-L) in human macrophages and elucidate the mechanism underlying CstF64-modulated MRJ isoform expression. Moreover, we exploited an antisense strategy targeting MRJ-L for virus replication. A morpholino oligonucleotide complementary to the 5' splice site of MRJ intron 8 downregulated MRJ-L expression and suppressed the replication of not only HIV-1 but also respiratory syncytial virus (RSV). We demonstrated that downregulation of the MRJ-L level reduced HIV-1 replication as well as the subgenomic mRNA and viral production of RSV. The present findings that two human health-threatening viruses take advantage of MRJ-L for infection suggest MRJ-L as a potential target for broad-spectrum antiviral strategy.
    日期: 2019-03-01
    關聯: Molecular Therapy. Nucleic Acids. 2019 Mar 1;14:251-261.
    Link to: http://dx.doi.org/10.1016/j.omtn.2018.12.001
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2162-2531&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000460323000020
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85059813421
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