藉由調控熱休克蛋白MRJ之多聚腺苷酸化機制來發展全方位抗病毒策略
Study of alternative polyadenylation as a regulatory mechanism of mammalian DnaJ (MRJ) and development of a broad-spectrum antiviral strategy through manipulation of MRJ
The molecular chaperon MRJ (DNAJB6) exhibits two splice isoforms that have different roles in human viral infection. In this study, 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 human immunodeficiency virus (HIV-1) but also respiratory syncytial virus (RSV). We demonstrated that downregulation of MRJ-L level reduced HIV-1 replication as well as the subgenomic mRNA and viral production of RSV. The present finding that two human health-threatening viruses take advantage of MRJ-L for infection suggests MRJ-L as a potential target for broad-spectrum antiviral strategy.
分子伴護蛋白質 MRJ (DNAJB6) 有兩種剪接之分子異構物, 並於人類病毒感染中扮演著不同地角色。於此研究中, 我們利用反股標的 MRJ-L 並觀察對於病毒複製所造成的影響。與 MRJ 內含子 8 的 5 端剪接位點互補的嗎啉核苷酸能抑制 MRJ-L 的表現並且減低人類免疫缺陷病毒 (HIV-1) 與人類呼吸道融合病毒 (RSV) 之複製能力。我們證明當 MRJ-L 之表現量下降同時也抑制了 HIV-1 之複製能力以及 RSV mRNA 與病毒顆粒之產生。MRJ-L 目前已對兩種威脅人類健康之病毒造成影響, 代表 MRJ-L 具有作為廣泛抗病毒策略之潛力。