SPF Rabbits Infected with Rabbit Hepatitis E Virus Isolate Experimentally Showing the Chronicity of Hepatitis

Abstract

This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits.

Hepatitis E vaccine immunization for rabbits to prevent animal HEV infection and zoonotic transmission

“…Prior to vaccination, all rabbits were confirmed negative for anti-HEV antibodies by an enzyme-linked immunosorbent assay (ELISA) and negative for HEV RNA in fecal/serum by RT-nPCR [40]. Each rabbit was placed in a separate cage and fed twice a day.…”

“…Accumulative lines of evidence have indicated that rabbits are sensitive to HEV infection and seem to constitute an animal reservoir of HEV [34,39]. The fact that rabbits can be experimentally infected by sHEV-4 [40] or human HEV-4 [41] and that rHEV is transmissible from rabbits to cynomolgus macaques [42] both suggest that rabbits may be a new source of human HEV infection. Interestingly, a HEV strain in rabbits closely related to human HEV strain has been identified in France [36], and recently, a HEV strain closely related to a human HEV sequence was identified for the first time in the pet house rabbit [43].…”

Extra-Hepatic Replication and Infection of Hepatitis E Virus in Neuronal-Derived Cells

“…Recently, rabbits were experimentally HEV-infected with a trend to chronic infection and positive/negative RNA as well as HEV antigen expression was observed in several organs including the brain (34). Possible pathological mechanisms of these extra-hepatic viral associations, however, have not been addressed and are difficult to directly compare with the disease in HEV-infected patients.…”

<b>Detecção e quantificação do vírus da hepatite E (HEV) por RT-PCR em tempo real e estudo experimental em primatas neotropicais (<i>Aotus azarai infulatus</i>) infectados pelo genótipo 3 do HEV</b>

“…Outro fator pode estar relacionado à replicação extra-hepática renal do HEV, que já foi demonstrada em coelhos infectados experimentalmente que apresentaram o tecido renal positivo para HEV-RNA, com imunomarcação positiva de antígenos virais e observação de infiltrado inflamatório intersticial no rins (HAN et al, 2014). Devido ao fato de não ter sido avaliado o tecido renal não pudemos confirmar se as alterações de marcadores de função renal estavam relacionadas à infecção pelo vírus e estudos subsequentes devem ser desenvolvidos para melhor caracterização de possíveis manifestações extra-hepáticas no modelo.…”

“…A técnica de imunohistoquímica já foi utilizada para detecção de antígenos do HEV no fígado de humanos (LAU et al, 1995;GUPTA et al, 2012), suínos (HA;CHAE, 2004;XIAO et al, 2012), javalis (NARDINI et al, 2014), macacos rhesus , gerbils YANG et al, 2015) e coelhos (HAN et al, 2014;MAO et al, 2014;.…”