title: Highly divergent hepaciviruses from African cattle.
abstract: The hepatitis C virus (HCV; genus Hepacivirus) is a highly relevant human pathogen. Unique hepaciviruses (HV) were discovered recently in animal hosts. The direct ancestor of HCV has not been found, but the genetically most closely related animal HVs exist in horses. To investigate whether other peridomestic animals also carry HVs, we analyzed sera from Ghanaian cattle for HVs by reverse transcription-PCR (RT-PCR). Nine of 106 specimens from different sampling sites contained HV RNA (8.5%) at median viral loads of 1.6 × 10(5) copies/ml. Infection seemed unrelated to cattle age and gender. Near-full-genome sequencing of five representative viruses confirmed taxonomic classifications. Cattle HVs formed two distinct phylogenetic lineages that differed by up to 17.7% on the nucleotide level in the polyprotein-encoding region, suggesting cocirculation of different virus subtypes. A conserved microRNA122-binding site in the 5' internal ribosomal entry site suggested liver tropism of cattle HVs. Phylogenetic analyses suggested the circulation of HVs in cattle for several centuries. Cattle HVs were genetically highly divergent from all other HVs, including HCV. HVs from genetically related equine and bovine hosts were not monophyletic, corroborating host shifts during the evolution of the genus Hepacivirus. Similar to equine HVs, the genetic diversity of cattle HVs was low compared to that of HCV genotypes. This suggests an influence of the human-modified ecology of peridomestic animals on virus diversity. Further studies should investigate the occurrence of cattle HVs in other geographic areas and breeds, virus pathogenicity in cattle, and the potential exposure of human risk groups, such as farmers, butchers, and abattoir workers.
  
  
  OBJECTIVE
  HCV (genus Hepacivirus) is a major human pathogen, causing liver failure and cancer. Unique hepaciviruses (HVs) were discovered over the last few years in animals, but the direct ancestor of HCV has not been found. The animal HV most closely related to HCV so far originated from horses, suggesting that other livestock animals also harbor HVs. Therefore, we investigated African cattle and discovered previously unknown HVs at high prevalence and viral loads. Because of the agricultural importance of cattle, it may be relevant to investigate HV pathogenicity. The frequent exposure of humans to cattle also may warrant investigations of the zoonotic potential of these viruses. Evolutionary analyses suggested that cattle HVs have existed for centuries. Despite the genetic relatedness of their animal hosts, HVs from cattle and horses were not phylogenetically related, corroborating frequent host shifts during the evolution of the genus Hepacivirus.
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany German Centre for Infection Research (DZIF), partner sites Bonn-Cologne, Hamburg-Lübeck-Borstel, and Hannover-Braunschweig, Germany.
authors: Victor Max
authors: VM
authors: Corman
authors: German Centre for Infection Research (DZIF), partner sites Bonn-Cologne, Hamburg-Lübeck-Borstel, and Hannover-Braunschweig, Germany Heinrich-Pette Institute, Leibniz Institute for Experimental Virology, Research Group Virus Genomics, Hamburg, Germany.
authors: Adam
authors: A
authors: Grundhoff
authors: German Centre for Infection Research (DZIF), partner sites Bonn-Cologne, Hamburg-Lübeck-Borstel, and Hannover-Braunschweig, Germany Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors: Christine
authors: C
authors: Baechlein
authors: German Centre for Infection Research (DZIF), partner sites Bonn-Cologne, Hamburg-Lübeck-Borstel, and Hannover-Braunschweig, Germany Institute for Medical Microbiology, Virology and Hygiene, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
authors: Nicole
authors: N
authors: Fischer
authors: Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow, Russia Lomonosov Moscow State University, Moscow, Russia.
authors: Anatoly
authors: A
authors: Gmyl
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
authors: Robert
authors: R
authors: Wollny
authors: Ghana Veterinary Service, Kumasi, Ghana.
authors: Dickson
authors: D
authors: Dei
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
authors: Daniel
authors: D
authors: Ritz
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany.
authors: Tabea
authors: T
authors: Binger
authors: Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
authors: Ernest
authors: E
authors: Adankwah
authors: Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
authors: Kwadwo Sarfo
authors: KS
authors: Marfo
authors: Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
authors: Lawrence
authors: L
authors: Annison
authors: Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana.
authors: Augustina
authors: A
authors: Annan
authors: Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors: Yaw
authors: Y
authors: Adu-Sarkodie
authors: Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
authors: Samuel
authors: S
authors: Oppong
authors: German Centre for Infection Research (DZIF), partner sites Bonn-Cologne, Hamburg-Lübeck-Borstel, and Hannover-Braunschweig, Germany Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
authors: Paul
authors: P
authors: Becher
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany German Centre for Infection Research (DZIF), partner sites Bonn-Cologne, Hamburg-Lübeck-Borstel, and Hannover-Braunschweig, Germany.
authors: Christian
authors: C
authors: Drosten
authors: Institute of Virology, University of Bonn Medical Centre, Bonn, Germany German Centre for Infection Research (DZIF), partner sites Bonn-Cologne, Hamburg-Lübeck-Borstel, and Hannover-Braunschweig, Germany drexler@virology-bonn.de.
authors: Jan Felix
authors: JF
authors: Drexler
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000821:virology*; D016000:Cluster Analysis; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D005869:Ghana; D016174:Hepacivirus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000662:veterinary* / Q000821:virology; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D044967:Serum / Q000821:virology; D019562:Viral Load
chemical_list: D012367:RNA, Viral