Hepatitis G virus genomic RNA is pathogenic to Macaca mulatta

Abstract

Aim: To explore the pathogenicity and infectivity of hepatitis G virus (HGV) by observing replication and expression of the virus, as well as the serological and histological changes of Macaca mulatta infected with HGV genomic RNA or HGV RNA-positive serum.

Methods: Full-length HGV cDNA clone (HGVqz) was constructed and proved to be infectious, from which HGV genomic RNA was transcribed in vitro. Macaca mulatta BY1 was intra-hepatically inoculated with HGV genomic RNA, HGV RNA-positive serum from BY1 was intravenously inoculated into Macaca mulatta BM1, and then BB1 was infected with serum from BM1. Serum and liver tissue were taken regularly, and checked with RT-PCR, in situ hybridization and other immunological, serological, histological assays.

Results: Serum HGV RNA was detectable in all the 3 Macaca mulattas, serological and histological examinations showed the experimental animals had slightly elevated alanine transaminase (ALT) and developed HGV viremia during the infectious period. The histology, immunohis-tochemistry, and in situ hybridization in liver tissues of the inoculated animals demonstrated a very mild hepatitis with HGV antigen expression in cytoplasm of hepatocytes. RT-PCR and quantitative PCR results showed that HGV could replicate in liver.

Conclusion: The genomic RNA from full-length HGV cDNA is infectious to the Macaca mulatta and can cause mild hepatitis. HGV RNA-positive serum, from HGV RNA inoculated Macaca mulatta, is infectious to other Macaca mulattas. Macaca mulatta is susceptible to the inoculated HGV, and therefore can be used as an experimental animal model for the studies of HGV infection and pathogenesis.

Figure 1

HGV RNA transcripts in vitro transcribed from plasmid pHGVqz. Lane 1: molecular standard, lane 2: T7 linear DNA control, lane 3: HGV genomic RNA.

Figure 2

ALT levels, anti-HGV and HGV RNA in inoculated Macaca mulattas.

Figure 3

Immunohistochemistry (A) and in situ hybridization (B) results of liver from inoculated Macaca mulattas. A1: Normal liver; A2, A3: HGV E2 protein in infected liver; B1: Normal liver; B2, B3: HGV mRNA in infected liver.