Differential Infection Patterns and Recent Evolutionary Origins of Equine Hepaciviruses in Donkeys

Abstract

The hepatitis C virus (HCV) is a major human pathogen. Genetically related viruses in animals suggest a zoonotic origin of HCV. The closest relative of HCV is found in horses (termed equine hepacivirus [EqHV]). However, low EqHV genetic diversity implies relatively recent acquisition of EqHV by horses, making a derivation of HCV from EqHV unlikely. To unravel the EqHV evolutionary history within equid sister species, we analyzed 829 donkeys and 53 mules sampled in nine European, Asian, African, and American countries by molecular and serologic tools for EqHV infection. Antibodies were found in 278 animals (31.5%), and viral RNA was found in 3 animals (0.3%), all of which were simultaneously seropositive. A low RNA prevalence in spite of high seroprevalence suggests a predominance of acute infection, a possible difference from the mostly chronic hepacivirus infection pattern seen in horses and humans. Limitation of transmission due to short courses of infection may explain the existence of entirely seronegative groups of animals. Donkey and horse EqHV strains were paraphyletic and 97.5 to 98.2% identical in their translated polyprotein sequences, making virus/host cospeciation unlikely. Evolutionary reconstructions supported host switches of EqHV between horses and donkeys without the involvement of adaptive evolution. Global admixture of donkey and horse hepaciviruses was compatible with anthropogenic alterations of EqHV ecology. In summary, our findings do not support EqHV as the origin of the significantly more diversified HCV. Identification of a host system with predominantly

Evolutionary biology of human hepatitis viruses

“…101 In horses, parenteral transmission of equine hepacivirus has been suggested, 102,103 possibly including sexual transmission and veterinary practices. 41,102 Transmission via human-aided routes would suggest a relatively recent spread of this virus among equines worldwide and is consistent with the low virus diversity found in equines. 38,41,102,104 Similar transmission routes are conceivable for cattle hepaciviruses.…”

“…41,102 Transmission via human-aided routes would suggest a relatively recent spread of this virus among equines worldwide and is consistent with the low virus diversity found in equines. 38,41,102,104 Similar transmission routes are conceivable for cattle hepaciviruses. 44,45 In sum, virus transmission seems to be evolutionary conserved among enteric hepatitis viruses and their homologues, while transmission routes of non-human hepadnaviruses and hepaciviruses are poorly understood.…”

“…[34][35][36][37] HCV-related viruses were detected in horses in 2012, and evidence for sporadic spill-over infections of the horse-associated viruses into dogs and donkeys was found. [38][39][40][41] Soon afterwards, highly diverse HCV-related viruses were detected in bats and rodents, 42,43 in cattle, 44,45 and in black-and-white colobus monkeys. 46 Hepatitis D-like agents were recently detected in ducks and snakes.…”

“…33 However, cross-species transmission must also have occurred during the evolution of hepatitis viruses. Apart from the zoonotic HEV genotypes, examples of cross-species transmission events include hepatoviruses in marsupials that are of likely rodent origin, 28 horse-associated hepaciviruses in dogs and donkeys, 38,41 gorillas infected with chimpanzee hepadnaviruses, orangutans infected with gibbon hepadnaviruses, 119 and rat hepeviruses in shrews. 204 In addition, the tentative HBV genotype J likely emerged from a recombination event involving human-and gibbon-associated parental strains, hinting at cross-species viral transmission from gibbons to humans (summarised in 80 ).…”

The phylogenomics of evolving virus virulence

“…Although this may sound straightforward and is tractable in some cases 25 , in reality it faces a number of difficulties. In many cases, including common infections such as hepatitis C virus 26 , as well as emerging infectious diseases such as Zika virus (ZIKV), the reservoir species is unknown or is at best uncertain. Even if a reservoir species is known, we generally know little, if anything, about virulence in that species, and there is likely to be an ascertainment bias towards the most virulent cases.…”