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.

分子伴侣MRJ（DNAJB6）表现出两种剪接同工型，在人类病毒感染中具有不同的作用，但是MRJ异构体表达的调控机制尚不清楚。在这项研究中，我们表明，聚腺苷酸化因子CstF64的减少与人类巨噬细胞中MRJ大同工型（MRJ-L）的增加有关，并阐明了CstF64调节MRJ同工型表达的机制。此外，我们利用针对MRJ-L的反义策略进行病毒复制。与MRJ 5'剪接位点互补的吗啉代寡核苷酸内含子8下调了MRJ-L的表达，不仅抑制了HIV-1的复制，还抑制了呼吸道合胞病毒（RSV）的复制。我们证明了MRJ-L水平的下调减少了HIV-1复制以及亚基因组mRNA和RSV的病毒产生。目前发现，两种威胁人类健康的病毒利用MRJ-L进行感染，这表明MRJ-L是广谱抗病毒策略的潜在目标。