Previous Article | Next Article 
J Virol, April 1998, p. 2589-2599, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Analysis of Hepatitis C Virus-Inoculated
Chimpanzees Reveals Unexpected Clinical Profiles
Suzanne E.
Bassett,1,2
Kathleen M.
Brasky,1 and
Robert E.
Lanford1,2,*
Department of Virology and Immunology,
Southwest Foundation for Biomedical Research, San Antonio, Texas
78227,1 and
Department of Microbiology,
University of Texas Health Science Center at San Antonio, San
Antonio, Texas 782842
Received 15 September 1997/Accepted 22 December 1997
The clinical course of hepatitis C virus (HCV) infections in a
chimpanzee cohort was examined to better characterize the outcome of
this valuable animal model. Results of a cross-sectional study revealed
that a low percentage (39%) of HCV-inoculated chimpanzees were viremic
based on reverse transcription (RT-PCR) analysis. A correlation was
observed between viremia and the presence of anti-HCV antibodies. The
pattern of antibodies was dissimilar among viremic chimpanzees and
chimpanzees that cleared the virus. Viremic chimpanzees had a higher
prevalence of antibody reactivity to NS3, NS4, and NS5. Since an
unexpectedly low percentage of chimpanzees were persistently infected
with HCV, a longitudinal analysis of the virological profile of a small
panel of HCV-infected chimpanzees was performed to determine the
kinetics of viral clearance and loss of antibody. This study also
revealed that a low percentage (33%) of HCV-inoculated chimpanzees
were persistently viremic. Analysis of serial bleeds from six
HCV-infected animals revealed four different clinical profiles. Viral
clearance with either gradual or rapid loss of anti-HCV antibody was
observed in four animals within 5 months postinoculation. A
chronic-carrier profile characterized by persistent HCV RNA and
anti-HCV antibody was observed in two animals. One of these chimpanzees
was RT-PCR positive, antibody negative for 5 years and thus represented
a silent carrier. If extrapolated to the human population, these data
would imply that a significant percentage of unrecognized HCV
infections may occur and that silent carriers may represent potentially
infectious blood donors.
*
Corresponding author. Mailing address: Department of
Virology and Immunology, Southwest Foundation for Biomedical Research, 7620 N.W. Loop 410, San Antonio, TX 78228. Phone: (210) 670-3245. Fax:
(210) 670-3329. E-mail: rlanford{at}icarus.sfbr.org.
This article has been cited by other articles:
-
Nainan, O. V., Lu, L., Gao, F.-X., Meeks, E., Robertson, B. H., Margolis, H. S.
(2006). Selective transmission of hepatitis C virus genotypes and quasispecies in humans and experimentally infected chimpanzees. J. Gen. Virol.
87: 83-91
[Abstract]
[Full Text]
-
Sugimoto, K., Kaplan, D. E., Ikeda, F., Ding, J., Schwartz, J., Nunes, F. A., Alter, H. J., Chang, K.-M.
(2005). Strain-Specific T-Cell Suppression and Protective Immunity in Patients with Chronic Hepatitis C Virus Infection. J. Virol.
79: 6976-6983
[Abstract]
[Full Text]
-
Sundstrom, S., Ota, S., Dimberg, L. Y., Masucci, M. G., Bergqvist, A.
(2005). Hepatitis C Virus Core Protein Induces an Anergic State Characterized by Decreased Interleukin-2 Production and Perturbation of Mitogen-Activated Protein Kinase Responses. J. Virol.
79: 2230-2239
[Abstract]
[Full Text]
-
Bergqvist, A., Sundstrom, S., Dimberg, L. Y., Gylfe, E., Masucci, M. G.
(2003). The Hepatitis C Virus Core Protein Modulates T Cell Responses by Inducing Spontaneous and Altering T-cell Receptor-triggered Ca2+ Oscillations. J. Biol. Chem.
278: 18877-18883
[Abstract]
[Full Text]
-
Nascimbeni, M., Mizukoshi, E., Bosmann, M., Major, M. E., Mihalik, K., Rice, C. M., Feinstone, S. M., Rehermann, B.
(2003). Kinetics of CD4+ and CD8+ Memory T-Cell Responses during Hepatitis C Virus Rechallenge of Previously Recovered Chimpanzees. J. Virol.
77: 4781-4793
[Abstract]
[Full Text]
-
Major, M. E., Mihalik, K., Puig, M., Rehermann, B., Nascimbeni, M., Rice, C. M., Feinstone, S. M.
(2002). Previously Infected and Recovered Chimpanzees Exhibit Rapid Responses That Control Hepatitis C Virus Replication upon Rechallenge. J. Virol.
76: 6586-6595
[Abstract]
[Full Text]
-
Schmidt, W., Stapleton, J. T., Knight, G. B., Agnello, V.
(2001). Whole-Blood Hepatitis C Virus RNA Extraction Methods. J. Clin. Microbiol.
39: 3812-3813
[Full Text]
-
Bigger, C. B., Brasky, K. M., Lanford, R. E.
(2001). DNA Microarray Analysis of Chimpanzee Liver during Acute Resolving Hepatitis C Virus Infection. J. Virol.
75: 7059-7066
[Abstract]
[Full Text]
-
Lanford, R. E., Lee, H., Chavez, D., Guerra, B., Brasky, K. M.
(2001). Infectious cDNA clone of the hepatitis C virus genotype 1 prototype sequence. J. Gen. Virol.
82: 1291-1297
[Abstract]
[Full Text]
-
Lu, L., Nakano, T., Orito, E., Mizokami, M., Robertson, B. H.
(2001). Evaluation of Accumulation of Hepatitis C Virus Mutations in a Chronically Infected Chimpanzee: Comparison of the Core, E1, HVR1, and NS5b Regions. J. Virol.
75: 3004-3009
[Abstract]
[Full Text]
-
Bergqvist, A., Rice, C. M.
(2001). Transcriptional Activation of the Interleukin-2 Promoter by Hepatitis C Virus Core Protein. J. Virol.
75: 772-781
[Abstract]
[Full Text]
-
Beames, B., Chavez, D., Guerra, B., Notvall, L., Brasky, K. M., Lanford, R. E.
(2000). Development of a Primary Tamarin Hepatocyte Culture System for GB Virus-B: a Surrogate Model for Hepatitis C Virus. J. Virol.
74: 11764-11772
[Abstract]
[Full Text]
-
Ray, S. C., Mao, Q., Lanford, R. E., Bassett, S., Laeyendecker, O., Wang, Y.-M., Thomas, D. L.
(2000). Hypervariable Region 1 Sequence Stability during Hepatitis C Virus Replication in Chimpanzees. J. Virol.
74: 3058-3066
[Abstract]
[Full Text]
-
Kolykhalov, A. A., Mihalik, K., Feinstone, S. M., Rice, C. M.
(2000). Hepatitis C Virus-Encoded Enzymatic Activities and Conserved RNA Elements in the 3' Nontranslated Region Are Essential for Virus Replication In Vivo. J. Virol.
74: 2046-2051
[Abstract]
[Full Text]
-
Liang, T. J., Rehermann, B., Seeff, L. B., Hoofnagle, J. H.
(2000). Pathogenesis, Natural History, Treatment, and Prevention of Hepatitis C. ANN INTERN MED
132: 296-305
[Abstract]
[Full Text]
-
Leyssen, P., De Clercq, E., Neyts, J.
(2000). Perspectives for the Treatment of Infections with Flaviviridae. Clin. Microbiol. Rev.
13: 67-82
[Abstract]
[Full Text]
-
Beld, M., Penning, M., van Putten, M., van den Hoek, A., Damen, M., Klein, M. R., Goudsmit, J.
(1999). Low Levels of Hepatitis C Virus RNA in Serum, Plasma, and Peripheral Blood Mononuclear Cells of Injecting Drug Users During Long Antibody-Undetectable Periods Before Seroconversion. Blood
94: 1183-1191
[Abstract]
[Full Text]
-
Ray, S. C., Wang, Y.-M., Laeyendecker, O., Ticehurst, J. R., Villano, S. A., Thomas, D. L.
(1999). Acute Hepatitis C Virus Structural Gene Sequences as Predictors of Persistent Viremia: Hypervariable Region 1 as a Decoy. J. Virol.
73: 2938-2946
[Abstract]
[Full Text]
-
Major, M. E., Mihalik, K., Fernandez, J., Seidman, J., Kleiner, D., Kolykhalov, A. A., Rice, C. M., Feinstone, S. M.
(1999). Long-Term Follow-Up of Chimpanzees Inoculated with the First Infectious Clone for Hepatitis C Virus. J. Virol.
73: 3317-3325
[Abstract]
[Full Text]
-
Bassett, S. E., Thomas, D. L., Brasky, K. M., Lanford, R. E.
(1999). Viral Persistence, Antibody to E1 and E2, and Hypervariable Region 1 Sequence Stability in Hepatitis C Virus-Inoculated Chimpanzees. J. Virol.
73: 1118-1126
[Abstract]
[Full Text]