Presence of a Novel Subtype of Bovine Hepacivirus in China and Expanded Classification of Bovine Hepacivirus Strains Worldwide into 7 Subtypes.

Gang Lu,Jiajun Ou,Shoujun Li,Jiawei Zhao

doi:10.3390/v11090843

Abstract

The newest member of the Hepacivirus genus, bovine hepacivirus (BovHepV), was first identified in cattle in 2015 and is a novel hepacivirus C virus (HCV)-like virus. This virus has been detected in five countries so far and is classified into four subtypes. Bovine serum is commonly used for cell cultures and is considered the major source of viral contamination of pharmaceutical products. In this study, bovine serum samples were collected from seven countries located in Asia, America, Oceania, and Europe and were tested for BovHepV RNA using nested PCR, in order to: (i) obtain more knowledge on the geographical distribution and subtypes of BovHepV; and (ii) detect the potential contamination of BovHepV in commercial bovine serum samples used for cell culture propagation. The results demonstrated that bovine serum samples from individual donor cattle in China contained BovHepV RNA. After PCR, sequencing, and assembly, the genomes of the Chinese BovHepV strains were obtained. Genetic analysis of the polyprotein gene revealed a protein identity of <77% and a nucleotide identity of <85% between the Chinese BovHepV strains and all other previously reported BovHepV strains. Using cut-off values for determination of HCV genotypes and subtypes, BovHepV strains worldwide were classified into one unique genotype and seven subtypes. The BovHepV strains identified in the present study were classified into a novel subtype, which was provisionally designated subtype G. The genetic relationships among the different BovHepV subtypes were further confirmed through phylogenetic analysis. The present study provides critical insights into BovHepV’s geographical distribution and genetic variability.

Highlights

Hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma, cirrhosis, and liver failure in humans
This study indicates the importance of testing bovine hepacivirus (BovHepV) in commercial bovine serum and increases our knowledge of the genetic diversity of BovHepV
Bovine viral diarrhea virus (BVDV) and bovine parvovirus contamination have been identified in commercial fetal bovine serum [23]

Summary

Introduction

Hepatitis C virus (HCV) is one of the leading causes of hepatocellular carcinoma, cirrhosis, and liver failure in humans. Chronic hepatitis C virus (HCV) infection is estimated to affect >185 million persons worldwide [1]. Humans were considered the only established hosts for viruses in the Hepacivirus genus. Since 2011, HCV-like homologs have been discovered in several animal hosts, such as dogs [2], equines [3], bats [4], rodents [5], cattle [6,7], monkeys [8], shrews [9], sharks [10], turtles [11], and fish [11]. The genomes of viruses in the Hepacivirus genus are linear, positive-sense single-stranded RNA genomes ~10 kb in size with a single long open reading frame (ORF) flanked by a 5’ untranslated As suggested by the International Committee on Taxonomy of Viruses (ICTV), the Hepacivirus genus can be assigned to fourteen species (Hepacivirus A–N) and is classified within the Flaviviridae family, together with the genera Flavivirus, Pegivirus, and Pestivirus [12].

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