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A Cell Culture Model for Producing High Titer Hepatitis E Virus Stocks
Published on: June 26, 2020
Different susceptibility and pathogenesis of rabbit genotype 3 hepatitis E virus (HEV-3) and human HEV-3 (JRC-HE3) in
Yulin Zhang1, Wanyun Gong1, William Tianshi Song1
1Department of Microbiology and Center of Infectious Disease, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Abstract:
Hepatitis E virus (HEV) is an increasingly important zoonotic infection in humans with HEV genotypes 3 and 4 being recognized as zoonotic pathogens. The relatively recently isolated genotype 3 rabbit HEV (rHEV-3) and the more well known genotype 3 isolates from humans and swine (hsHEV-3) have all been confirmed experimentally to be capable of infecting both non-human primates and specific-pathogen free (SPF) pigs. In a previous study rHEV-3 was shown to cause acute hepatitis in experimentally infected rabbits. However, whether hsHEV-3 can productively infect rabbits remained unclear. The objective of this study was to investigate the experimental infection of rabbits with human HEV-3 (hHEV-3, JRC-HE3), to compare it to that with rHEV-3 (CHN-BJ-rb14) and to further characterise the pathogenesis of the two isolates. All animals inoculated with rHEV-3 (CHN-BJ-rb14) became infected, exhibiting an intermittent viremia, elevated liver enzymes, and persistent fecal virus shedding throughout the 15 week study period. Liver histopathology showed acute inflammation and both positive- and negative-stranded viral RNA was detected in various tissues from necropsied rabbits. By contrast, neither sero-conversion nor alanine aminotransferase (ALT) elevation was observed in most rabbits inoculated with hHEV-3 (JRC-HE3). In addition, rHEV-3 (CHN-BJ-rb14) but not hHEV-3 (JRC-HE3) recovered from primary infected rabbits was transmissible to naive rabbits. These results showed that SPF rabbits are readily susceptible to infection with rHEV-3 (CHN-BJ-rb14) but not hHEV-3 (JRC-HE3), which might indicate the influence of viral genomic organization on its pathogenicity.
Insights
Specific-pathogen-free (SPF) rabbits are susceptible to rabbit Hepatitis E virus genotype 3 (rHEV-3) but not human HEV genotype 3 (hHEV-3). This suggests viral genomic organization influences HEV pathogenicity in rabbits.
Area of Science:
- Veterinary Virology
- Zoonotic Diseases
- Hepatitis E Virus Research
Background:
- Hepatitis E virus (HEV) genotypes 3 and 4 are significant zoonotic pathogens.
- Rabbit HEV genotype 3 (rHEV-3) and human/swine HEV genotype 3 (hsHEV-3) infect non-human primates and pigs.
- Previous studies confirmed rHEV-3 causes hepatitis in rabbits, but hsHEV-3's rabbit infectivity was unknown.
Purpose of the Study:
- To investigate experimental infection of rabbits with human HEV genotype 3 (hHEV-3).
- To compare hHEV-3 infection with rabbit HEV genotype 3 (rHEV-3) infection.
- To further characterize the pathogenesis of both HEV isolates in rabbits.
Main Methods:
- Experimental inoculation of specific-pathogen-free (SPF) rabbits with rHEV-3 (CHN-BJ-rb14) and hHEV-3 (JRC-HE3).
- Monitoring for viremia, elevated liver enzymes (ALT), and fecal virus shedding.
- Histopathological examination of liver tissues and detection of viral RNA.
- Transmission studies to naive rabbits.
Main Results:
- All rabbits inoculated with rHEV-3 (CHN-BJ-rb14) showed infection, viremia, elevated ALT, and persistent fecal shedding.
- rHEV-3 infected rabbits exhibited acute liver inflammation and viral RNA in tissues.
- Most rabbits inoculated with hHEV-3 (JRC-HE3) did not seroconvert or show ALT elevation.
- rHEV-3 was transmissible to naive rabbits, whereas hHEV-3 was not.
Conclusions:
- SPF rabbits are highly susceptible to rHEV-3 (CHN-BJ-rb14) infection.
- SPF rabbits are resistant to productive infection by hHEV-3 (JRC-HE3).
- Viral genomic organization may influence HEV pathogenicity and host tropism in rabbits.
