Abstract

The hepatitis E virus (HEV) is one of the main causes of enterically transmitted hepatitis worldwide. Although the mortality rates associated with HEV are generally low, they can be up to 28% in HEV-infected pregnant women, and the elderly are more susceptible. The reasons for this selective severity are unclear, partially because there is no suitable, easy-to-use model in which to study HEV infection. Non-human primates and standard swine have been identified as being sensitive to infection with HEV and have been used for HEV infection studies. However, studies in these animals have been limited by high housing costs and the difficulty of manipulating these animals. In the current study, we established a model of HEV infection using Bama miniature swine. The model is easy to use and is sensitive to infections with HEV genotypes 3 and 4, which are classified as zoonotic HEVs. In this model, infection of Bama miniature swine with HEV genotypes 3 and 4 caused the typical features. All Bama miniature swine that were infected with HEV genotypes 3 and 4 exhibited significant HEV viremia, shedding, anti-HEV antibody responses and partial liver inflammation. Bama miniature swine may serve as an alternative to standard swine models for the study of zoonotic HEV infection and HEV genotype specificity research.

Highlights

  • The hepatitis E virus (HEV), which causes human hepatitis E, is an important pathogen worldwide[1,2,3]

  • All swine were confirmed to be free of HEV through testing their feces using real-time PCR (GenMagBio, Beijing, China) and free of serum anti-HEV antibodies via testing with an HEV Ab kit (Wantai, Beijing, China) prior to inoculation

  • The miniature swine were injected with a viral titer of 1.35 × 107 genomic equivalents (GE) per mL of the viral genotype for the group to which they were assigned, and the control group swine were injected with 1 mL of phosphate-buffered saline (PBS, pH 7.4)

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Summary

Introduction

The hepatitis E virus (HEV), which causes human hepatitis E, is an important pathogen worldwide[1,2,3]. Standard swine have been experimentally infected with HEV genotypes 3 and 4, and the HEV-infected swine shed the viruses in their feces for several weeks[13]. Chinese Bama miniature swine are genetically stable, highly inbred, and small[14,15,16] These animals are easier to handle than larger domestic swine. Compared with Bama miniature swine, the cost of non-human primates was [10,11,12,13,14,15,16,17,18,19,20] times higher in China, and the cost of standard swine is [3,4] times higher. Positive (+)or negative (−) for HEV antigens/HEV RNA detection in the feces/HEV RNA detection in the serum/anti-HEV antibody detection in the serum in the indicated week post-inoculation

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