- 作者: Gregory R. Reyes
- 作者服務機構: Infectious Diseases and Oncology, Schering-Plough Research Institute, Kenilworth, NJ., USA
- 中文摘要: --
- 英文摘要: transcription activation machinery and cell cycle-regula-tory kinases have been described (e.g. growth factorreceptor-bound protein 2, p53, p21/waf and cyclins).Many of these interactions block the apoptotic cellularresponse to persistent HCV infection. More recently,another altogether different mechanism attenuating theIFN-α response was reported based on induction of inter-leukin (IL)-8. IL-8, in model systems, potentiates viralreplication and mutes the nonspecific intracellular IFNantiviral response. Evidence supporting a complex mul-timechanistic role of NS5A in promoting viral persis-tence, pathogenesis and, indirectly, viral-related hepato-carcinogenesis indicates its key role in HCV pathobi-ology.The hepatitis C virus (HCV) NS5A gene product is a phos-phorylated 56- to 58-kD nonstructural protein that dis-plays a multitude of activities related to enhancement ofviral pathogenesis. Although associated with other viralencoded proteins as part of the viral replicase complexpositioned on the cytoplasmic side of the endoplasmicreticulum, a role for NS5A in viral replication has notbeen defined. Post-translationa∣modifications of NS5Ainclude phosphorylation and potential proteolytic pro-cessing to smaller molecular weight forms able to trans-locate to the nucleus. Both the identification of a putativeinterferon (IFN) sensitivity-determining region withinNS5A, as well as the direct interaction with and inhibitionof the IFN-induced double-stranded RNA-dependent pro-tein kinase (PKR) by NS5A remain controversial. Trun-cated versions of NS5A can act as transcriptional activa-tors, while other recently characterized interactions ofNS5A with cellular proteins indicate its pleiotropic role inHCV-host interactions. NS5A itself has no direct effect onIFN-a signaling or activation, but other abundant interac-tions with members of the cellular signaling apparatus,
- 中文關鍵字: --
- 英文關鍵字: Hepatitis C virus, NS5A, Interferon-a, PKR, Interferon sensitivity-determining region, Viral pathogenesis