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Journal of Virology, January 2000, p. 805-811, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Nucleotide and Amino Acid Complexity of Hepatitis C Virus Quasispecies in Serum and Liver

Beatriz Cabot, María Martell, Juan I. Esteban,* Sílvia Sauleda, Teresa Otero, Rafael Esteban, Jaime Guàrdia, and Jordi Gómez

Liver Unit, Department of Internal Medicine, Hospital General Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, 08035 Barcelona, Spain

Received 15 July 1999/Accepted 19 October 1999

The quasispecies nature of the hepatitis C virus (HCV) is thought to play a central role in maintaining and modulating viral replication. Several studies have tried to unravel, through the parameters that characterize HCV circulating quasispecies, prognostic markers of the disease. In a previous work we demonstrated that the parameters of circulating viral quasispecies do not always reflect those of the intrahepatic virus. Here, we have analyzed paired serum and liver quasispecies from 39 genotype 1b-infected patients with different degrees of liver damage, ranging from minimal changes to cirrhosis. Viral level was quantified by real-time reverse transcription-PCR, and viral heterogeneity was characterized through the cloning and sequencing of 540 HCV variants of a genomic fragment encompassing the E2-NS2 junction. Although in 95% of patients, serum and liver consensus HCV amino acid sequences were identical, quasispecies complexity varied considerably between the viruses isolated from each compartment. Patients with HCV quasispecies in serum more complex (26%) than, less complex (28%) than, or similarly complex (41%) to those in liver were found. Among the last, a significant correlation between fibrosis and all the parameters that measure the viral amino acid complexity was found. Correlation between fibrosis and serum viral load was found as well (R = 0.7). With regard to the origin of the differences in quasispecies complexity between serum and liver populations, sequence analysis argued against extrahepatic replication as a quantitatively important contributing factor and supported the idea of a differential effect or different selective forces on the virus depending on whether it is circulating in serum or replicating in the liver.

* Corresponding author. Mailing address: Laboratori de Medicina Interna-Hepatologia, Unitat B d'Investigació (Edifici de Magatzems Generals), Hospital Vall d'Hebron, Passeig Vall d'Hebron 119, 08035 Barcelona, Spain. Phone: 34-93 4894934. Fax: 34-93 4894032. E-mail: jgomez{at}hg.vhebron.es.

Journal of Virology, January 2000, p. 805-811, Vol. 74, No. 2
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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