Hepatitis C virus--cell interactions and their role in pathogenesis.
In summary, HCV-cell interactions include those directly involved with the HCV life cycle such as virus attachment, entry, and replication. Included within this broad area of research are the interactions of HCV proteins with the IFN system, cytokine and chemokine pathways such as IL-8, and various other cellular proteins and pathways. The plethora of contradictory and sometimes confusing accessory HCV-host interactions defies precise predictions of their role in HCV biology. It is clear that these virus-cell interactions affect HCV replication, antiviral resistance, persistence, and pathogenesis. Because HCV-host interactions are initiated immediately on infection, they are operative during acute HCV infection, whereby HCV interacts with innate cellular antiviral and immune systems. The magnitude and duration of these HCV-host interactions therefore may influence the development of acquired immunity. Because HCV exists as a quasispecies in all infected individuals, heterogeneity in biological responses to HCV-host interactions is predicted, revealing opportunities for the development of various genotypic and phenotypic prognostic indicators. With the model systems in place, these hypotheses can be tested. The challenge for the future is to determine if there is a hierarchical importance to these interactions, to delineate how these virus-cell interactions affect the patient infected with HCV, and to determine whether any of these interactions represents a target for therapeutic intervention.
Polyak
Stephen J
SJ
Department of Laboratory Medicine, University of Washington, Box 359690, 325 9th Avenue, Seattle, WA 98104-2499, USA. polyak@u.washington.edu
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D002450:Cell Communication / Q000502:physiology*; D018450:Disease Progression; D016174:Hepacivirus / Q000472:pathogenicity* / Q000502:physiology; D006526:Hepatitis C / Q000821:virology*; D006801:Humans
D000998:Antiviral Agents