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Microbiology spectrum2022; 10(5); e0168622; doi: 10.1128/spectrum.01686-22

Dose-Dependent Hepacivirus Infection Reveals Linkage between Infectious Dose and Immune Response.

Abstract: 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 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. We demonstrate that the EqHV dose of infection plays an important role for inducing immune responses, possibly linked to early clearance in high-dose and prolonged viremia in low-dose infections. In particular, pathways associated with innate and adaptive immune responses, as well as inflammatory responses, were more strongly upregulated in high-dose infections than in lower doses. Hence, inoculation with low doses may enable EqHV to evade strong immune responses in the early phase and therefore promote robust, long-lasting infection.
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Publication Date: 2022-08-22 PubMed ID: 35993785PubMed Central: PMC9602444DOI: 10.1128/spectrum.01686-22Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research study investigates the connection between the dose of equine hepacivirus (EqHV) infection and immune response in horses. The researchers discovered that the level of infection dose plays a crucial role in triggering immune responses, therefore affecting how quickly the infection is cleared or prolonged.

Study Design and Process

  • The researchers inoculated eight horses that had not been previously exposed to EqHV with varying doses – ranging from one to two copies to a high of 1.3 x 10 RNA copies per inoculation.
  • They then monitored the infection kinetics, pathology and responses at the transcriptomic level using next-generation sequencing techniques. The aim was to determine the minimum infectious dose, examine how it related to the duration of infection and seroconversion, and assess the corresponding transcriptomic responses.

Key Findings

  • The researchers estimated that the minimum infectious dose of EqHV in horses was around 13 RNA copies. When less than that, 6-7 RNA copies, were administered, it was insufficient to cause a productive infection.
  • Peak viremia or virus level in blood did not correlate directly with the infectiousness of the dose. However, the process of seroconversion – when the body starts producing detectable antibodies against the virus – and the duration of infection were found to be affected by the dose.
  • In low-dose infections, seroconversion was undetectable within the standard surveillance period of 40-50 days. This significant latency in immune response potentially makes it easier for EqHV to prolong robust and longer-lasting infection in affected animals.
  • On the other hand, high-dose infections witnessed greater immune activation and inflammatory response, which was reflected in the transcriptomic analysis.
  • Interestingly, even doses (6-7 copies) which did not result in a productive infection, triggered a strong immune response, akin to that observed in high-dose infections.

Implications of the Study

  • The study highlights the importance of the dose in hepacivirus infection, showing that it significantly influences the immune response. This could be potentially linked to how quickly the virus is cleared in high-dose infections and why viremia extends for a longer duration in low-dose infections.
  • The clear correlation between dose and various immune response factors could inform the development of vaccinations and treatments for hepacivirus, a global health challenge that remains unsolved.

Cite This Article

APA
Gömer A, Delarocque J, Puff C, Nocke MK, Reinecke B, Baumgärtner W, Cavalleri JMV, Feige K, Steinmann E, Todt D. (2022). Dose-Dependent Hepacivirus Infection Reveals Linkage between Infectious Dose and Immune Response. Microbiol Spectr, 10(5), e0168622. https://doi.org/10.1128/spectrum.01686-22

Publication

Microbiology spectrum
ISSN: 2165-0497
NlmUniqueID: 101634614
Country: United States
Language: English
Volume: 10
Issue: 5
Pages: e0168622
PII: e01686-22

Researcher Affiliations

Gömer, André
  • Department of Molecular and Medical Virology, Ruhr University Bochumgrid.5570.7, Bochum, Germany.
  • Institute of Virology, University of Veterinary Medicine Hannover, Hanover, Germany.
Delarocque, Julien
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hanover, Germany.
Puff, Christina
  • Department of Pathology, University of Veterinary Medicine Hannover, Hanover, Germany.
Nocke, Maximilian K
  • Department of Molecular and Medical Virology, Ruhr University Bochumgrid.5570.7, Bochum, Germany.
Reinecke, Birthe
  • Institute of Experimental Virology, TWINCORE Centre for Experimental and Clinical Infection Research, Hanover, Germany.
Baumgärtner, Wolfgang
  • Department of Pathology, University of Veterinary Medicine Hannover, Hanover, Germany.
Cavalleri, Jessika M V
  • Clinical Section of Equine Internal Medicine, Department of Companion Animals and Horses, University of Veterinary Medicine Viennagrid.6583.8, Vienna, Austria.
Feige, Karsten
  • Clinic for Horses, University of Veterinary Medicine Hannover, Hanover, Germany.
Steinmann, Eike
  • Department of Molecular and Medical Virology, Ruhr University Bochumgrid.5570.7, Bochum, Germany.
Todt, Daniel
  • Department of Molecular and Medical Virology, Ruhr University Bochumgrid.5570.7, Bochum, Germany.
  • European Virus Bioinformatics Center (EVBC), Jena, Germany.

MeSH Terms

  • Horses / genetics
  • Animals
  • Hepacivirus / genetics
  • Viremia
  • Horse Diseases / epidemiology
  • Phylogeny
  • Immunity
  • RNA

Conflict of Interest Statement

The authors declare no conflict of interest.

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Citations

This article has been cited 3 times.
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