Experimental infection of Z:ZCLA Mongolian gerbils with human hepatitis E virus

Abstract

Aim: To investigate whether Z:ZCLA Mongolian gerbils are readily susceptible to infection by human hepatitis E virus (HEV).

Methods: Z:ZCLA Mongolian gerbils were infected with a clinical HEV strain isolated from an acute hepatitis E patient, and virus pathogenesis was assessed in this host. Non-infected gerbils served as the control group. Feces samples from gerbils were collected weekly for reverse transcription-nested polymerase chain reaction. Serum anti-HEV IgG and alanine aminotransferase (ALT) were detected by enzyme linked immunosorbent assay. At sacrifice, each animal's liver, spleen and kidney were collected for histopathologic examination.

Results: HEV-infected gerbils showed fatigue, with histopathological changes observed in the liver, spleen and kidney. HEV RNA was detected in fecal samples taken at day 7 after inoculation and the detectable levels lasted out to day 42 after inoculation. Interestingly, ALT levels were only moderately increased in the HEV-infected animals compared with the non-infected control group.

Conclusion: Z:ZCLA Mongolian gerbils are susceptible to human HEV.

Keywords: Hepatitis E virus; Infection; Interspecies transmission; Mongolian gerbils; Zoonosis.

Figure 1

Changes in alanine aminotransferase levels after hepatitis E virus infection. Z:ZCLA Mongolian gerbils showed alanine aminotransferase (ALT) level changes upon hepatitis E virus infection. The ALT levels were moderately increased in the inoculated group compared with the control group at days 14 and 21 post-inoculation. No changes were observed in the control group.

Figure 2

Reverse transcription-nested polymerase chain reaction detection of viral shedding in feces. Hepatitis E virus RNA was detected by reverse transcription-nested polymerase chain reaction (RT-nPCR) in feces from all inoculated gerbils. Lane M: DNA marker; Lanes 1-6 represent experimental time points (in weeks): the second round PCR products of gerbil feces samples on intermittent days; Lane 7: a negative control containing water.

Figure 3

Histopathologic changes in the hepatitis E virus-inoculated Mongolian gerbils. A: A representative liver sample showing slight histiocytic hepatitis and focal accumulation of inflammatory cells surrounding hepatocytes [21 d post-inoculation (DPI)]; B: A representative spleen sample showing ruptured and enlarged splenocytes with multiple vacuolar degeneration (21 DPI); C: A representative kidney showing disarranged kidney cells with increased infiltrating lymphocytes and macrophages (35 DPI); D: A representative negative control liver; E: A representative negative control spleen; F: A representative Negative control kidney. All tissues were stained with hematoxylin and eosin. Original magnifications × 400.