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Journal of Virology, May 2005, p. 6349-6357, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6349-6357.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Compartmentalization of Hepatitis C Virus Genotypes between Plasma and Peripheral Blood Mononuclear Cells

Anne-Marie Roque-Afonso,1,2 Delphine Ducoulombier,2 Gaëtana Di Liberto,3 Rachid Kara,2 Michele Gigou,2 Elisabeth Dussaix,1,2 Didier Samuel,2 and Cyrille Féray3*

Laboratoire de Virologie, Hôpital Paul Brousse, 12 avenue Paul Vaillant-Couturier, Villejuif 94804, France,1 Unité Propre de Recherche Enseignement Supérieur (UPRES 3541), Paris XI, Centre Hépato Biliaire, Hôpital Paul Brousse,2 Institut National de la Santé et de la Recherche Médicale (INSERM) U-481, Faculté de Médecine Xavier Bichat, 16 rue Henri Huchard, Paris 75018, France3

Received 4 October 2004/ Accepted 3 January 2005

Differences in hepatitis C virus (HCV) variants of the highly conserved 5' untranslated region (UTR) have been observed between plasma and peripheral blood mononuclear cells (PBMC). The prevalence and the mechanisms of this compartmentalization are unknown. Plasma and PBMC HCV variants were compared by single-strand conformation polymorphism (SSCP) and by cloning or by genotyping with a line probe assay (LiPA) in 116 chronically infected patients, including 44 liver transplant recipients. SSCP patterns differed between compartments in 43/109 analyzable patients (39%). Differences were significantly more frequent in patients with transplants (21/38 [55%] versus 22/71 [31%]; P < 0.01) and in those who acquired HCV through multiple transfusions before 1991 (15/20; 75%) or through drug injection (16/31; 52%) than in those infected through an unknown route (7/29; 24%) or through a single transfusion (5/29; 17%; P < 0.001). Cloning of the 5' UTR, LiPA analysis, and nonstructural region 5B sequencing revealed different genotypes in the two compartments from 10 patients (9%). In nine patients, the genotype detected in PBMC was not detected in plasma and was weak or undetectable in the liver in three cases. This genotypic compartmentalization persisted for years in three patients and after liver transplantation in two. The present study shows that a significant proportion of HCV-infected subjects harbor in their PBMC highly divergent variants which were likely acquired through superinfections.

* Corresponding author. Mailing address: INSERM U-481, Faculté Xavier Bichat, 16 rue Henri Huchard, Paris 75018, France. Phone: 33144856198. Fax: 011-33-144859279. E-mail: Feray{at}bichat.inserm.fr.

Journal of Virology, May 2005, p. 6349-6357, Vol. 79, No. 10
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.10.6349-6357.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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