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Revisiting the Mongolian Gerbil Model for Hepatitis E Virus by Reverse Genetics.

Ling-Dong Xu1, Fei Zhang2, Chu Chen1

  • 1Department of Veterinary Medicine, Zhejiang Universitygrid.13402.34, Hangzhou, China.

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|March 1, 2022
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Summary

Researchers validated the Mongolian gerbil as a small animal model for Hepatitis E virus (HEV) infection, enabling new antiviral drug development and immune response studies for this significant human pathogen.

Keywords:
Mongolian gerbilantiviralshepatitis E virus (HEV)innate immunityinterferonreverse genetics

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Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Hepatitis E virus (HEV) is a significant cause of acute viral hepatitis globally.
  • A lack of suitable small animal models hinders HEV research and antiviral development.
  • Previous studies on gerbil susceptibility to HEV were inconsistent.

Purpose of the Study:

  • To validate and characterize the Mongolian gerbil as a small animal model for human HEV genotypes 1, 3, and 4.
  • To assess the utility of the gerbil model for antiviral drug testing.
  • To investigate host innate immune responses to HEV infection in vivo.

Main Methods:

  • Utilized HEV reverse genetics to generate infectious RNA transcripts for genotypes 1, 3, and 4.
  • Inoculated Mongolian gerbils intrahepatically and intraperitoneally with HEV.
  • Monitored HEV infection markers including viral load in tissues and feces, seroconversion, and liver pathology.
  • Evaluated antiviral efficacy of peg-IFNα-2a and ribavirin.
  • Investigated host immune response using TBK1 inhibitors.

Main Results:

  • Gerbils infected with genotype 3 HEV RNA or cloned virus showed robust infection, with HEV detected in liver, spleen, and feces for up to 7 weeks.
  • Infection was confirmed by seroconversion and observable pathological liver lesions.
  • Peg-IFNα-2a and ribavirin demonstrated efficacy in inhibiting HEV replication in gerbils.
  • The study identified a role for RIG-I-like receptor-interferon regulatory factor 3 in anti-HEV innate immunity.
  • Genotype 4 HEV was susceptible in gerbils, while genotype 1 showed no susceptibility.

Conclusions:

  • The Mongolian gerbil is a validated and convenient small animal model for studying human HEV genotypes 3 and 4.
  • This model is effective for evaluating antiviral therapies against HEV.
  • The gerbil model facilitates the study of host innate immune mechanisms against HEV infection.
  • This research provides a crucial tool for advancing HEV antiviral development and understanding host-pathogen interactions.