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Can I read In Vitro and In Vivo Stability of P884T, a Mutation that Relocalizes Dengue Virus 2 Non-structural Protein 5 on EtoBox?
In Vitro and In Vivo Stability of P884T, a Mutation that Relocalizes Dengue Virus 2 Non-structural Protein 5 by Colin X. Cheng; Min Jie Alvin Tan; Kitti W. K. Chan; Satoru Watanabe; Sai Wang; Milly M. Choy; Menchie Manuel; Carla B. L. Victorio; Joanne Ong; Marie Reolo; Ann-Marie Chacko; Subhash G. Vasudevan is a Medicine article available to read on EtoBox.
What is In Vitro and In Vivo Stability of P884T, a Mutation that Relocalizes Dengue Virus 2 Non-structural Protein 5 about?
Dengue virus (DENV) non-structural protein 5 (NS5) is critical for viral RNA synthesis within endoplasmic reticulum (ER)-derived replication complexes in the cytoplasm; however a proportion of NS5 is known to be localized to the nucleus of infected cells. The importance of nuclear DENV NS5 on viral replication and pathogenesis is still unclear. We recently discovered a nuclear localization signal (NLS) residing in the Cterminal 18 amino acid (Cter 18 ) region of DENV NS5 and that a single NS5 P884T amino acid substitution adjacent to the NLS is sufficient to relocalize a significant proportion of DENV2 NS5 from the nucleus to the cytoplasm of infected cells. Here, in vitro studies show that the DENV2 NS5 P884T mutant replicates similarly to the parental wild-type infectious clone-derived virus while inducing a greater type I interferon and inflammatory cytokine response, in a manner independent of NS5's ability to degrade STAT2 or regulate SAT1 splicing. In both AG129 mouse and Aedes aegypti mosquito infection models, the P884T virus exhibits lower levels of viral replication only at early timepoints. Intriguingly, there appears to be a tendency for selection pressure to revert to
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- Author
- Colin X. Cheng; Min Jie Alvin Tan; Kitti W. K. Chan; Satoru Watanabe; Sai Wang; Milly M. Choy; Menchie Manuel; Carla B. L. Victorio; Joanne Ong; Marie Reolo; Ann-Marie Chacko; Subhash G. Vasudevan
- Publisher
- American Chemical Society (ACS)
- Published
- 2021
- Language
- EN
- Field
- Medicine (Life Sciences)