Previous Article | Next Article 
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.
This article has been cited by other articles:
-
Howe, A. Y. M., Cheng, H., Johann, S., Mullen, S., Chunduru, S. K., Young, D. C., Bard, J., Chopra, R., Krishnamurthy, G., Mansour, T., O'Connell, J.
(2008). Molecular Mechanism of Hepatitis C Virus Replicon Variants with Reduced Susceptibility to a Benzofuran Inhibitor, HCV-796. Antimicrob. Agents Chemother.
52: 3327-3338
[Abstract]
[Full Text]
-
Howe, A. Y. M., Cheng, H., Thompson, I., Chunduru, S. K., Herrmann, S., O'Connell, J., Agarwal, A., Chopra, R., Del Vecchio, A. M.
(2006). Molecular Mechanism of a Thumb Domain Hepatitis C Virus Nonnucleoside RNA-Dependent RNA Polymerase Inhibitor. Antimicrob. Agents Chemother.
50: 4103-4113
[Abstract]
[Full Text]
-
Jouvencel, A.-C., Neau, D., Faure, M., Neau, M., Martinaud, C., Legrand, E., Trimoulet, P., Garrigue, I., Le Bail, B., Bioulac-Sage, P., Dupon, M., Ragnaud, J.-M., Fleury, H., Lafon, M.-E.
(2006). Plasma and liver hepatitis C virus variability in patients coinfected with human immunodeficiency virus.. J. Clin. Microbiol.
44: 1877-1880
[Abstract]
[Full Text]
-
Jridi, C., Martin, J.-F., Marie-Jeanne, V., Labonne, G., Blanc, S.
(2006). Distinct Viral Populations Differentiate and Evolve Independently in a Single Perennial Host Plant. J. Virol.
80: 2349-2357
[Abstract]
[Full Text]
-
Roque-Afonso, A.-M., Ducoulombier, D., Di Liberto, G., Kara, R., Gigou, M., Dussaix, E., Samuel, D., Feray, C.
(2005). Compartmentalization of Hepatitis C Virus Genotypes between Plasma and Peripheral Blood Mononuclear Cells. J. Virol.
79: 6349-6357
[Abstract]
[Full Text]
-
Piron, M., Beguiristain, N., Nadal, A., Martinez-Salas, E., Gomez, J.
(2005). Characterizing the function and structural organization of the 5' tRNA-like motif within the hepatitis C virus quasispecies. Nucleic Acids Res
33: 1487-1502
[Abstract]
[Full Text]
-
Cormier, E. G., Durso, R. J., Tsamis, F., Boussemart, L., Manix, C., Olson, W. C., Gardner, J. P., Dragic, T.
(2004). L-SIGN (CD209L) and DC-SIGN (CD209) mediate transinfection of liver cells by hepatitis C virus. Proc. Natl. Acad. Sci. USA
101: 14067-14072
[Abstract]
[Full Text]
-
Forton, D. M., Karayiannis, P., Mahmud, N., Taylor-Robinson, S. D., Thomas, H. C.
(2004). Identification of Unique Hepatitis C Virus Quasispecies in the Central Nervous System and Comparative Analysis of Internal Translational Efficiency of Brain, Liver, and Serum Variants. J. Virol.
78: 5170-5183
[Abstract]
[Full Text]
-
Cormier, E. G., Tsamis, F., Kajumo, F., Durso, R. J., Gardner, J. P., Dragic, T.
(2004). CD81 is an entry coreceptor for hepatitis C virus. Proc. Natl. Acad. Sci. USA
101: 7270-7274
[Abstract]
[Full Text]
-
Wodarz, D.
(2003). Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses. J. Gen. Virol.
84: 1743-1750
[Abstract]
[Full Text]
-
Nadal, A., Robertson, H. D., Guardia, J., Gomez, J.
(2003). Characterization of the structure and variability of an internal region of hepatitis C virus RNA for M1 RNA guide sequence ribozyme targeting. J. Gen. Virol.
84: 1545-1548
[Abstract]
[Full Text]
-
Nadal, A., Martell, M., Lytle, J. R., Lyons, A. J., Robertson, H. D., Cabot, B., Esteban, J. I., Esteban, R., Guardia, J., Gomez, J.
(2002). Specific Cleavage of Hepatitis C Virus RNA Genome by Human RNase P. J. Biol. Chem.
277: 30606-30613
[Abstract]
[Full Text]
-
Curran, R., Jameson, C. L., Craggs, J. K., Grabowska, A. M., Thomson, B. J., Robins, A., Irving, W. L., Ball, J. K.
(2002). Evolutionary trends of the first hypervariable region of the hepatitis C virus E2 protein in individuals with differing liver disease severity. J. Gen. Virol.
83: 11-23
[Abstract]
[Full Text]
-
Cabot, B., Martell, M., Esteban, J. I., Piron, M., Otero, T., Esteban, R., Guardia, J., Gomez, J.
(2001). Longitudinal Evaluation of the Structure of Replicating and Circulating Hepatitis C Virus Quasispecies in Nonprogressive Chronic Hepatitis C Patients. J. Virol.
75: 12005-12013
[Abstract]
[Full Text]