Alternative splicing of ybx1 gene and its effects on dengue virus replication.

• Main Author: Lee, Junhong.
• Other Authors: School of Biological Sciences
• Format: Final Year Project
• Language: English
• Published: 2012
• Subjects: DRNTU::Science::Biological sciences::Microbiology::Virology; DRNTU::Science::Biological sciences::Molecular biology
• Online Access: http://hdl.handle.net/10356/48779
• Institution: Nanyang Technological University

Dengue is a serious health problem in many countries around the world without an effective preventive measure. An incomplete understanding of dengue pathogenesis has complicated vaccine development. Particularly, it is not known how host response to dengue virus (DENV) infection influence infection outcome. An on-going study of alternative splicing of genes in DENV-infected Huh-7 cells has shown Y-box-binding protein-1 (YBX1), which may have antiviral properties, has splice isoforms that are differentially regulated during DENV infection. Here, it was confirmed through qPCR that three of its splice isoforms (YBX1-2, YBX1-3 and YBX1-4) are differentially regulated during infection by both wild-type DENV1 16007 and its attenuated derivative, DENV1 PDK-13. These splice isoforms were uniformly up-regulated in DENV1 16007 infection, but YBX1-2 and YBX1-3 showed reduced levels with DENV1 PDK13. This observation suggests that DENV1 PDK13, but not DENV1 16007, is susceptible to the antiviral effects of YBX1-2 and YBX1-3. Overexpression of these three splice isoforms in Huh-7 cells confirmed the antiviral effect of YBX1-3 on DENV1 PDK-13 but not the parental wild-type DENV-1 16007. Given that YBX-1 binds to the viral RNA, this study suggests that mutation in the viral genome affects the efficacy of the host antiviral response to DENV infection.