The hepatitis C virus enigma.
Hepatitis C virus (HCV) has a high propensity to establish chronic infection with end-stage liver disease. The high turnover of virus particles and high transcription error rates due to lack of proof-reading function of the viral polymerase imply that HCV exists as quasispecies, thus enabling the virus to evade the host immune response. Clearance of the virus is characterized by a multispecific, vigorous and persistent T-cell response, whereas T-cell responses are weak, narrow and transient in patients who develop chronic infection. At present, standard treatment is a combination of pegylated interferon-alpha and ribavirin, with a sustained viral response rate of 40-80%, depending on genotype. The mechanisms for the observed synergistic effects of the two drugs are still not known in detail, but in addition to direct antiviral mechanisms, the immunomodulatory effects of both drugs seem to be important, with a shift from Th2- to Th1-cytokine profiles in successfully treated patients. This article describes virus-host relations in the natural course of HCV infection and during treatment.
Myrmel
Helge
H
Department of Microbiology and Immunology, Haukeland University Hospital, Bergen, Norway. helge.myrmel@haukeland.no
Ulvestad
Elling
E
Asjø
Birgitta
B
D015703:Antigens, CD / Q000502:physiology; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D005075:Biological Evolution; D018450:Disease Progression; D004357:Drug Synergism; D016174:Hepacivirus / Q000187:drug effects / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology / Q000821:virology*; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000209:etiology; D008113:Liver Neoplasms / Q000209:etiology; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D011991:Receptors, Virus / Q000502:physiology; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D060225:Tetraspanin 28; D014761:Viral Hepatitis Vaccines; D014766:Viremia / Q000276:immunology / Q000821:virology; D014779:Virus Replication
D015703:Antigens, CD; D000998:Antiviral Agents; C554798:CD81 protein, human; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011991:Receptors, Virus; D011994:Recombinant Proteins; D060225:Tetraspanin 28; D014761:Viral Hepatitis Vaccines; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a