title: Evolution and function of the HCV NS3 protease in patients with acute hepatitis C and HIV coinfection.
abstract: Little is known about the importance of the hepatitis C virus (HCV) NS3 protease in acute hepatitis C. In this prospective study, 82 consecutive patients with acute hepatitis C and human immunodeficiency virus (HIV) coinfection were enrolled. Individuals were infected with highly related HCV strains and the baseline NS3 quasispecies diversity and complexity was higher compared to a chronic hepatitis C control group (P<0.0001). Both parameters were comparable in patients with spontaneous clearance (n=6) versus treatment-induced SVR (n=5) or development of chronic hepatitis C (n=9). Longitudinal NS3 quasispecies kinetics showed a trend to a decreasing diversity and complexity (P<0.05) within 4 weeks in patients with spontaneous clearance compared to the other groups. The innate immune signalling protein CARDIF was cleaved to a similar extent independent of the outcome. Together with a more pronounced viral load decline (P<0.05), an early decreasing NS3 quasispecies evolution indicates spontaneous clearance of acute hepatitis C.
authors: Department of Internal Medicine 1, J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Julia
authors: J
authors: Dietz
authors: Infektiologikum, Frankfurt, Germany.
authors: Thomas
authors: T
authors: Lutz
authors: Infektiologikum, Frankfurt, Germany.
authors: Gaby
authors: G
authors: Knecht
authors: Infektiologikum, Frankfurt, Germany.
authors: Peter
authors: P
authors: Gute
authors: Department of Internal Medicine 1, J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Caterina
authors: C
authors: Berkowski
authors: Department of Internal Medicine 1, J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Christian Markus
authors: CM
authors: Lange
authors: Department of Internal Medicine 2, J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Pavel
authors: P
authors: Khaykin
authors: Department of Internal Medicine 2, J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Christoph
authors: C
authors: Stephan
authors: Department of Internal Medicine 2, J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Hans-Reinhard
authors: HR
authors: Brodt
authors: Institute of Biostatistics and Mathematical Modeling, J.W. Goethe University, Frankfurt, Germany.
authors: Eva
authors: E
authors: Herrmann
authors: Department of Internal Medicine 1, J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Stefan
authors: S
authors: Zeuzem
authors: Department of Internal Medicine 1, J.W. Goethe University Hospital, Frankfurt, Germany. Electronic address: sarrazin@em.uni-frankfurt.de.
authors: Christoph
authors: C
authors: Sarrazin
mesh_terms: D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D060085:Coinfection; D019143:Evolution, Molecular; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000175:diagnosis / Q000821:virology*; D016174:Hepacivirus / Q000235:genetics*; D006526:Hepatitis C / Q000175:diagnosis / Q000821:virology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D010802:Phylogeny; D011446:Prospective Studies; D059748:Proteolysis; D016865:Reassortant Viruses / Q000235:genetics; D017361:Viral Nonstructural Proteins / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D017361:Viral Nonstructural Proteins; C505371:MAVS protein, human; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: Acute hepatitis C; CARDIF; Hepatitis C virus; Human immunodeficiency virus; NS3 protease; Quasispecies evolution; Spontaneous clearance