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Longitudinal analysis of hepatitis C virus infection and genetic drift of the hypervariable region
L J van Doorn1, W Quint, K Tsiquaye
1Diagnostic Center SSDZ, Delft, Netherlands.
Insights
Hepatitis C virus (HCV) RNA detection and antibody profiles were studied in chimpanzees. Chronic infections showed persistent HCV RNA, while acute infections resolved, highlighting immune selection
Area of Science:
- Virology
- Immunology
- Infectious Diseases
Background:
- Hepatitis C virus (HCV) is a significant global health concern.
- Understanding HCV infection dynamics in animal models is crucial for developing effective treatments and vaccines.
- Chimpanzees serve as a relevant model for studying HCV pathogenesis due to their susceptibility to infection.
Purpose of the Study:
- To retrospectively analyze Hepatitis C virus (HCV) infections in a cohort of chimpanzees.
- To investigate the viral RNA kinetics and antibody responses following experimental HCV inoculation.
- To examine the genetic stability and mutation patterns of the HCV genome during transmission and infection.
Main Methods:
- Retrospective analysis of HCV-infected chimpanzee cohort.
- Intravenous inoculation with ultracentrifuged chimpanzee plasma.
- Monitoring of HCV RNA using RNA-capture polymerase chain reaction.
- Detection of anti-HCV antibodies via confirmatory line immunoassay.
- Analysis of the E2/NS1 hypervariable region for genetic variations.
Main Results:
- HCV RNA was detectable post-inoculation, with varying kinetics in chronic versus resolving infections.
- Chronically infected chimpanzees exhibited persistent HCV RNA, while acute infections resolved with undetectable RNA post-normalization of alanine aminotransferase.
- Diverse anti-HCV antibody profiles were observed across the chimpanzee cohort.
- Analysis of the E2/NS1 hypervariable region indicated genome stability upon transmission but varied mutation frequencies during chronic infection.
Conclusions:
- Chimpanzee model provides insights into HCV infection dynamics, including viral RNA persistence and resolution.
- Immune selection appears to play a significant role in shaping HCV evolution during chronic infection.
- Genome stability during transmission and subsequent mutation frequencies are important factors in HCV pathogenesis.
Abstract:
Hepatitis C virus (HCV) infections in a cohort of chimpanzees were studied retrospectively. All animals had been inoculated intravenously with materials derived from a single-source chimpanzee plasma implicated in non-A, non-B hepatitis, prepared by extensive ultracentrifugation. Anti-HCV and HCV RNA were monitored by the confirmatory line immunoassay and by an RNA-capture polymerase chain reaction method, respectively. In a chronically infected chimpanzee, HCV RNA was detectable after 32 days and throughout the acute phase, dropped transiently below detection level, and became detectable again. In 3 other chimpanzees with acute resolving infections, HCV RNA was detected 7-11 days after inoculation and became permanently undetectable after alanine aminotransferase normalization. Various anti-HCV profiles were detected among the chimpanzees. Analysis of the hypervariable region in E2/NS1 in 7 chimpanzees suggested genome stability on transmission, revealed different mutation frequencies during chronic infection, and suggested the importance of immune selection during chronic HCV infection.