Interactions between influenza A virus NS1 protein and cellular PSMB4 protein
| Autor: | Hsu, Che-Fang, 許澤方 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Influenza A virus non-structural protein (NS1) is a multifunctional protein, which can modulate host-cell environment by interacting with its cellular proteins while the virus infected cells.NS1 inhibits host gene expression through interacting with cell nucleus mRNA polyadenylation factors (CPSF and PABII) and inhibits Intracytoplasmic Pathogen Sensor, RIG-I (retinoic acid-inducible gene I) to avoid immune response. In this study, Homo sapiens proteasome (prosome, macropain) subunit, beta type, 4 (PSMB4)was found to interact with NS1 protein and their binding domains were mapped using yeast two-hybrid system. Interaction between there two proteins were further proved by co-immunoprecipitation and confocal analysis assay.PSMB4 is 20S proteasome β subunits that are predominantly catalytic in ubiquitin-proteasome pathway .Based on confocal analysis assay, the interactions between these two proteins vary at differat state of virus infection. 18 hrs after infection, NS1 obviously interacted with PSMB4 in nucleus and restricted PSMB4 in the nucleus. In the later stages of infection, NS1 didn’t interact with PSMB4 in nucleus, and PSMB4 could be detected in the cytoplasm.Inhibition of cellular proteasome degradation pathway by virus infection was demonstrate either by the level of total protein ubiquitination or by one specific proteasome degraded protein-TopoII.We also demonstrated that inhibiting proteasome degradation pathway slightly (low concentration of MG132 or Lentiviral RNA knockdown PSMB4)could enhance the viral protein expression and viral particle production. However, inhibiting proteasome degradation pathway severely (e.g.high conc.of MG132) would suppress the viral protein expression and viral particle production. Our results demonstrate that influenza A virus NS1 protein could modulate cellular proteasome degradation pathway and in turn this effect could enhance the viral protein expression and viral particle production at the early stage virus infection. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|