title: High resistance of human parainfluenza type 2 virus protein-expressing cells to the antiviral and anti-cell proliferative activities of alpha/beta interferons: cysteine-rich V-specific domain is required for high resistance to the interferons.
abstract: Human parainfluenza type 2 virus (hPIV-2)-infected HeLa (HeLa-CA) cells and hPIV-2 V-expressing HeLa (HeLa-V) cells show high resistance to alpha/beta interferons (IFN-alpha/beta) irrespective of whether vesicular stomatitis virus or Sindbis virus is used as a challenge virus. When Sindbis virus is used, these cells show high susceptibility to human IFN-gamma. Furthermore, the multiplication of HeLa-V cells is not inhibited by IFN-alpha/beta. HeLa cells expressing the N-terminally truncated V protein show resistance to IFN-alpha/beta, showing that the IFN resistance determinant maps to the cysteine-rich V-specific domain. A complete defect of Stat2 is found in HeLa-CA and HeLa-V cells, whereas the levels of Stat1 expression are not significantly different among HeLa, HeLa-CA, HeLa-P, and HeLa-V cells, indicating that IFN-alpha/beta resistance of HeLa-CA and HeLa-V cells is due to a defect of Stat2. HeLa-SV41V cells show high resistance to all IFNs, and no expression of Stat1 can be detected. Stat2 mRNA is fully detected in HeLa-V cells. Stat2 was scarcely pulse-labeled in the HeLa-V cells, indicating that synthesis of Stat2 is suppressed or Stat2 is very rapidly degraded in HeLa-V cells. The V protein suppresses the in vitro translation of Stat2 mRNA more extensively than that of Stat1 mRNA. An extremely small amount of Stat2 can be detected in HeLa-V cells treated with proteasome inhibitors. The half-life of Stat2 is approximately 3.5 and 2 h in uninfected and hPIV-2-infected HeLa cells, respectively. This study shows that synthesis of Stat2 may be suppressed and Stat2 degradation is also enhanced in hPIV-2-infected HeLa and HeLa-V cells.
authors.affiliation: Department of Microbiology, Mie University School of Medicine, Tsu-Shi, Mie-Ken 514-8507, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishio
authors.forename: M
authors.initials: M
authors.lastname: Tsurudome
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Kawano
authors.forename: H
authors.initials: H
authors.lastname: Komada
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D003545:Cysteine; D004268:DNA-Binding Proteins / Q000502:physiology; D004352:Drug Resistance, Microbial; D006367:HeLa Cells; D006801:Humans; D007372:Interferons / Q000494:pharmacology* / Q000627:therapeutic use; D010223:Parainfluenza Virus 2, Human / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D019351:Rubulavirus Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators; D007372:Interferons; D003545:Cysteine