Interference of DNAJB6/MRJ Isoform Switch by Morpholino Inhibits Replication of HIV-1 and RSV
Journal
Molecular Therapy - Nucleic Acids
Journal Volume
14
Pages
251-261
Date Issued
2019
Author(s)
Abstract
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. ? 2018 The Author(s)
SDGs
Other Subjects
beta actin; chaperone; cleavage stimulation factor; cleavage stimulation factor 64; dnaj hsp40 family member b6 protein; glyceraldehyde 3 phosphate dehydrogenase; m2 1 protein; messenger RNA; messenger RNA precursor; morpholino oligonucleotide; nonstructural protein 1; ribonucleoprotein; serine arginine rich protein; srsf1 protein; srsf2 protein; srsf3 protein; unclassified drug; viral protein; alternative RNA splicing; antisense therapy; Article; controlled study; correlation coefficient; down regulation; drug targeting; gene expression regulation; HEK293T cell line; HEp-2 cell line; human; human cell; Human immunodeficiency virus 1; Human respiratory syncytial virus; intron; macrophage; monocyte; mRNA expression level; nonhuman; normal human; polyadenylation; priority journal; protein expression level; RNA 3' end processing; THP-1 cell line; virus genome; virus inhibition; virus replication
Publisher
Cell Press
Type
journal article