Dose-dependent hepacivirus infection reveals linkage between infectious dose and immune response
- More than 70 million people worldwide are still infected with the hepatitis C virus 30 years after its discovery, underscoring the need for a vaccine. To develop an effective prophylactic vaccine, detailed knowledge of the correlates of protection and an immunocompetent surrogate model are needed. In this study, we describe the minimum dose required for robust equine hepacivirus (EqHV) infection in equids and examined how this relates to duration of infection, seroconversion, and transcriptomic responses. To investigate mechanisms of hepaciviral persistence, immune response, and immune-mediated pathology, we inoculated eight EqHV naive horses with doses ranging from 1–2 copies to 1.3 × \(10^{6}\) RNA copies per inoculation. We characterized infection kinetics, pathology, and transcriptomic responses via next generation sequencing. The minimal infectious dose of EqHV in horses was estimated at 13 RNA copies, whereas 6 to 7 copies were insufficient to cause infection. Peak viremia did not correlate with infectious dose, while seroconversion and duration of infection appeared to be affected. Notably, seroconversion was undetectable in the low-dose infections within the surveillance period (40 to 50 days). In addition, transcriptomic analysis revealed a nearly dose-dependent effect, with greater immune activation and inflammatory response observed in high-dose infections than in low-dose infections. Interestingly, inoculation with 6–7 copies of RNA that did not result in productive infection, but was associated with a strong immune response, similar to that observed in the high-dose infections.
Author: | André Philipp GömerORCiDGND, Julien DelarocqueORCiDGND, Christina PuffGND, Maximilian K. NockeORCiDGND, Birthe Maren ReineckeORCiDGND, Wolfgang BaumgärtnerORCiDGND, Jessika CavalleriORCiDGND, Karsten FeigeGND, Eike SteinmannORCiDGND, Daniel Matthias TodtORCiDGND |
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URN: | urn:nbn:de:hbz:294-102625 |
DOI: | https://doi.org/10.1128/spectrum.01686-22 |
Parent Title (English): | Microbiology spectrum |
Publisher: | ASM |
Place of publication: | Birmingham, Großbritannien |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2023/10/20 |
Date of first Publication: | 2022/08/22 |
Publishing Institution: | Ruhr-Universität Bochum, Universitätsbibliothek |
Tag: | Open Access Fonds clearance and persistence; dose-dependent infection; hepacivirus; immune response; minimal infectious dose |
Volume: | 10 |
Issue: | 5 |
First Page: | 1 |
Last Page: | 13 |
Note: | Article Processing Charge funded by the Deutsche Forschungsgemeinschaft (DFG) and the Open Access Publication Fund of Ruhr-Universität Bochum. |
Institutes/Facilities: | Institut für Hygiene und Mikrobiologie, Abteilung für Molekulare und Medizinische Virologie |
Institut für Hygiene und Mikrobiologie | |
Medizinische Fakultät, Abteilung für Molekulare und Medizinische Virologie | |
Dewey Decimal Classification: | Naturwissenschaften und Mathematik / Biowissenschaften, Biologie, Biochemie |
open_access (DINI-Set): | open_access |
faculties: | Medizinische Fakultät |
Licence (English): | Creative Commons - CC BY 4.0 - Attribution 4.0 International |