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Journal of Virology, May 2005, p. 6023-6034, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6023-6034.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Human Serum Facilitates Hepatitis C Virus Infection, and Neutralizing Responses Inversely Correlate with Viral Replication Kinetics at the Acute Phase of Hepatitis C Virus Infection

Dimitri Lavillette,1 Yoann Morice,2 Georgios Germanidis,3 Peggy Donot,1 Alexandre Soulier,2 Emanuil Pagkalos,3 Georgios Sakellariou,4 Liliane Intrator,5 Birke Bartosch,1 Jean-Michel Pawlotsky,2 and François-Loïc Cosset1*

Laboratoire de Vectorologie Rétrovirale et Thérapie Génique, IFR128 BioSciences Lyon-Gerland, Ecole Normale Supérieure de Lyon, Lyon,1 Department of Virology, INSERM U635,2 Department of Immunology, Hôpital Henri Mondor, Université Paris XII, Créteil, France,5 Department of Internal Medicine,3 Department of Nephrology, Papageorgiou General Hospital, Thessaloniki, Greece4

Received 20 August 2004/ Accepted 17 November 2004

The factors leading to spontaneous clearance of hepatitis C virus (HCV) or to viral persistence are elusive. Understanding virus-host interactions that enable acute HCV clearance is key to the development of more effective therapeutic and prophylactic strategies. Here, using a sensitive neutralization assay based on infectious HCV pseudoparticles (HCVpp), we have studied the kinetics of humoral responses in a cohort of acute-phase patients infected during a single nosocomial outbreak in a hemodialysis center. The 17 patients were monitored for the spontaneous outcome of HCV infection for 6 months before a treatment decision was made. Blood samples were taken frequently (15 ± 4 per patient). Phylogenetic analysis of the predominant virus(es) revealed infection by only one of two genotype 1b strains. While all patients seroconverted, their sera induced two opposing effects in HCVpp infection assays: inhibition and facilitation. Furthermore, the ability of sera to facilitate or inhibit infection correlated with the presence of either infecting HCV strain and divided the patients into two groups. In group 1, the progressive emergence of a relatively strong neutralizing response correlated with a fluctuating decrease in high initial viremia, leading to control of viral replication. Patients in group 2 failed to reduce viremia within the acute phase, and no neutralizing responses were detected despite seroconversion. Strikingly, sera of group 2, as well as naïve sera, facilitated infection by HCVpp displaying HCV glycoproteins from different genotypes and strains, including those retrieved from patients. These results provide new insights into the mechanisms of viral persistence and immune control of viremia.

* Corresponding author. Mailing address: LVRTG, ENS de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France. Phone: 33 472 72 87 32. Fax: 33 472 72 80 80. E-mail: flcosset{at}ens-lyon.fr.

Journal of Virology, May 2005, p. 6023-6034, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6023-6034.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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