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Journal of Virology, November 1999, p. 9213-9221, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Nonrandom Distribution of Hepatitis C Virus Quasispecies in Plasma and Peripheral Blood Mononuclear Cell Subsets

Anne Marie Roque Afonso,1,2 Jiaji Jiang,1 François Penin,3 Claire Tareau,1 Didier Samuel,1 Marie-Anne Petit,1 Henri Bismuth,1 Elisabeth Dussaix,2 and Cyrille Féray1,*

Centre Hépato-Biliaire, Laboratoire de Recherche, Equipe Mixte INSERM (Institut National de la Santé et de la Recherche Médicale) 9941,1 and Laboratoire de Microbiologie, Université de Paris-Sud, Faculté de Médecine de Bicêtre, Assistance Publique-Hôpitaux de Paris, UPRES EA 1596, Hôpital Paul Brousse,2 94804 Villejuif, and Laboratoire de Conformation des Protéines, Institut de Biologie et Chimie des Protéines, Centre National de Recherche Scientifique, 69367 Lyon,3 France

Received 20 April 1999/Accepted 2 July 1999

The existence of an extrahepatic reservoir of hepatitis C virus (HCV) is suggested by differences in quasispecies composition between the liver, peripheral blood mononuclear cells, and serum. We studied HCV RNA compartmentalization in the plasma of nine patients, in CD19+, CD8+, and CD4+ positively selected cells, and also in the negatively selected cell fraction (NF). HCV RNA was detected in all plasma samples, in seven of nine CD19+, three of eight CD8+, and one of nine CD4+ cell samples, and in seven of eight NF cells. Cloning and sequencing of HVR1 in two patients showed a sequence grouping: quasispecies from a given compartment (all studied compartments for one patient and CD8+ and NF for the other) were statistically more genetically like each other than like quasispecies from any other compartment. The characteristics of amino acid and nucleotide substitutions suggested the same structural constraints on HVR1, even in very divergent strains from the cellular compartments, and homogeneous selection pressure on the different compartments. These findings demonstrate the compartmental distribution of HCV quasispecies within peripheral blood cell subsets and have important implications for the study of extrahepatic HCV replication and interaction with the immune system.

* Corresponding author. Mailing address: Hôpital Paul Brousse, 14 Ave. Paul Vaillant-Couturier, 94800 Villejuif, France. Phone: 33(1)45593749. Fax: 33(1)45593857. E-mail: cyrille.feray{at}pbr.ap-hp-paris.fr.

Journal of Virology, November 1999, p. 9213-9221, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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