An Immunocompetent Mongolian Gerbil Model for Hepatitis E Virus Genotype 1 Infection.
Gastroenterology
; 167(4): 750-763.e10, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-38582270
ABSTRACT
BACKGROUND & AIMS:
Hepatitis E virus (HEV), primarily genotype 1 (HEV-1), causes approximately 20.1 million infections, 44,000 deaths, and 3000 stillbirths annually. Current evidence indicates that HEV-1 is only transmitted in humans. Here, we evaluated whether Mongolian gerbils can serve as animal models for HEV-1 infection.METHODS:
Mongolian gerbils were used for HEV-1 and hepatitis E virus genotype 3 infection experiments. HEV infection parameters, including detection of HEV RNA and HEV antigen, liver function assessment, and histopathology, were evaluated.RESULTS:
We adapted a clinical isolate of HEV-1 for Mongolian gerbils by serial passaging in feces of aged male gerbils. The gerbil-adapted strain obtained at passage 3 induced a robust, acute HEV infection, characterized by stable fecal virus shedding, elevated liver enzymes, histopathologic changes in the liver, and seroconversion to anti-HEV. An infectious complementary DNA clone of the adapted virus was generated. HEV-1-infected pregnant gerbils showed a high rate of maternal mortality and vertical transmission. HEV RNA or antigens were detected in the liver, kidney, intestine, placenta, testis, and fetus liver. Liver and placental transcriptomic analyses indicated activation of host immunity. Tacrolimus prolonged HEV-1 infection, whereas ribavirin cleared infection. The protective efficacy of a licensed HEV vaccine was validated using this model.CONCLUSIONS:
HEV-1 efficiently infected Mongolian gerbils. This HEV-1 infection model will be valuable for investigating hepatitis E immunopathogenesis and evaluating vaccines and antivirals against HEV.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
RNA, Viral
/
Gerbillinae
/
Hepatitis E virus
/
Hepatitis E
/
Disease Models, Animal
/
Genotype
/
Immunocompetence
/
Liver
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
Gastroenterology
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Estados Unidos