Nonprimate Hepaciviruses in Domestic Horses, United Kingdom

Lyons, Sinéad; Kapoor, Amit; Sharp, Colin; Schneider, Bradley S.; Wolfe, Nathan; Culshaw, Geoff; Corcoran, Brendan; McGorum, Bruce; Simmonds, Peter

doi:10.3201/eid1812.120498

Cited by 103 publications

(151 citation statements)

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“…Similar to previous NPHV prevalence studies (4)(5)(6), we found 3-5% of horses with NPHV viremia except for one herd with an unexplained high prevalence of ∼40%. Viral RNA titers in serum were comparable to those found for HCV (31).…”

Section: Discussionsupporting

confidence: 90%

“…Nonprimate hepacivirus (NPHV) was the first to be discovered, initially identified in samples from dogs and termed canine hepacivirus (2). However, with the exception of a single seropositive farm dog (3), subsequent studies did not detect viral RNA or antibodies in dogs (4)(5)(6). Instead, horses appear to be the natural host for NPHV, with 30-40% antibody positive (4, 7) and 2-7% RNA positive among US and European horses (4-7) and an even higher RNA prevalence (35%) in a small Japanese herd (8).…”

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confidence: 99%

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Characterization of nonprimate hepacivirus and construction of a functional molecular clone

Scheel

Kapoor

Nishiuchi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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133

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Nonprimate hepacivirus (NPHV) is the closest known relative of hepatitis C virus (HCV) and its study could enrich our understanding of HCV evolution, immunity, and pathogenesis. High seropositivity is found in horses worldwide with ∼3% viremic. NPHV natural history and molecular virology remain largely unexplored, however. Here, we show that NPHV, like HCV, can cause persistent infection for over a decade, with high titers and negative strand RNA in the liver. NPHV is a near-universal contaminant of commercial horse sera for cell culture. The complete NPHV 3′-UTR was determined and consists of interspersed homopolymer tracts and an HCV-like 3′-terminal poly(U)-X-tail. NPHV translation is stimulated by miR-122 and the 3′-UTR and, similar to HCV, the NPHV NS3-4A protease can cleave mitochondrial antiviral-signaling protein to inactivate the retinoic acid-inducible gene I pathway. Using an NPHV consensus cDNA clone, replication was not observed in primary equine fetal liver cultures or after electroporation of selectable replicons. However, intrahepatic RNA inoculation of a horse initiated infection, yielding high RNA titers in the serum and liver. Delayed seroconversion, slightly elevated circulating liver enzymes and mild hepatitis was observed, followed by viral clearance. This establishes the molecular components of a functional NPHV genome. Thus, NPHV appears to resemble HCV not only in genome structure but also in its ability to establish chronic infection with delayed seroconversion and hepatitis. This NPHV infectious clone and resulting acute phase sera will facilitate more detailed studies on the natural history, pathogenesis, and immunity of this novel hepacivirus in its natural host.hepatitis C virus | infectious cDNA clone | equine liver disease | animal model | 3′-untranslated region

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

Characterization of nonprimate hepacivirus and construction of a functional molecular clone

Scheel

Kapoor

Nishiuchi

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

133

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“…assay was not necessary as described by Lyons et al (2012), which indicates a high amount of viral nucleic acid in sera. In addition, the high level of viraemia was also confirmed by the low level of crossing threshold (Ct) by real-time PCR.…”

Section: Resultsmentioning

confidence: 99%

“…Blood samples were separated by centrifugation and frozen at -80 °C until reverse transcription-PCR (RT-PCR) testing. Specific primer pairs (EQNS5BIS/ EQNS5BOIAS) were used for detection of nonstructural protein NS5B of NPHV by RT-PCR described previously (Lyons et al, 2012) (Table 1). Specific reverse or forward primers were designed based on the available NPHV sequences to determine the complete viral genome by RT-PCR (Table 1).…”

Section: Methodsmentioning

confidence: 99%

Non-primate hepacivirus infection with apparent hepatitis in a horse — Short communication

Reuter

Maza

Pankovics

et al. 2014

Acta Veterinaria Hungarica

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“…44 million heads, according to the Food and Agriculture Organization of the United Nations [FAO], FAOSTAT 2014 database). Donkeys have been tested for HV in limited numbers, such as 116 donkeys from the United Kingdom (17,20), 30 mules and 5 donkeys from Brazil (21), and 8 mules and 6 donkeys from China (22), as well as a commercially available donkey serum from the United States (23), all with negative results. Here we investigated a considerably larger panel of donkey sera from various countries using serologic and molecular tools.…”

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confidence: 99%

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

Wälter

Rasche

Moreira-Soto

et al. 2017

J Virol

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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

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Nonprimate Hepaciviruses in Domestic Horses, United Kingdom

Abstract: Viruses related to human hepatitis C virus infect horses in the United Kingdom without evidence of hepatic or other systemic disease.

Cited by 103 publications

References 32 publications

Characterization of nonprimate hepacivirus and construction of a functional molecular clone

Characterization of nonprimate hepacivirus and construction of a functional molecular clone

Non-primate hepacivirus infection with apparent hepatitis in a horse — Short communication

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

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