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Journal of Virology, February 1999, p. 1118-1126, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Viral Persistence, Antibody to E1 and E2, and Hypervariable Region 1 Sequence Stability in Hepatitis C Virus-Inoculated Chimpanzees

Suzanne E. Bassett,1,2 David L. Thomas,3 Kathleen M. Brasky,4 and Robert E. Lanford1,2,*

Department of Virology and Immunology1 and Department of Laboratory and Animal Medicine,4 Southwest Foundation for Biomedical Research, San Antonio, Texas 78227; Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 782842; and Division of Infectious Diseases, The Johns Hopkins School of Medicine, Baltimore, Maryland3

Received 22 May 1998/Accepted 26 October 1998

The relationship of viral persistence, the immune response to hepatitis C virus (HCV) envelope proteins, and envelope sequence variability was examined in chimpanzees. Antibody reactivity to the HCV envelope proteins E1 or E2 was detected by enzyme-linked immunosorbent assay (ELISA) in more than 90% of a human serum panel. Although the ELISAs appeared to be sensitive indicators of HCV infection in human serum panels, the results of a cross-sectional study revealed that a low percentage of HCV-inoculated chimpanzees had detectable antibody to E1 (22%) and E2 (15%). Viral clearance, which was recognized in 28 (61%) of the chimpanzees, was not associated with an antibody response to E1 or E2. On the contrary, antibody to E2 was observed only in viremic chimpanzees. A longitudinal study of animals that cleared the viral infection or became chronically infected confirmed the low level of antibody to E1, E2, and the HVR-1. In 10 chronically infected animals, the sequence variation in the E2 hypervariable region (HVR-1) was minimal and did not coincide with antibody to E2 or to the HVR-1. In addition, low nucleotide and amino acid sequence variation was observed in the E1 and E2 regions from two chronically infected chimpanzees. These results suggest that mechanisms in addition to the emergence of HVR-1 antibody escape variants are involved in maintaining viral persistence. The significance of antibodies to E1 and E2 in the chimpanzee animal model is discussed.


* 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.


Journal of Virology, February 1999, p. 1118-1126, Vol. 73, No. 2
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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