The Strange, Expanding World of Animal Hepaciviruses

Hartlage, Alex S.; Cullen, John M.; Kapoor, Amit

doi:10.1146/annurev-virology-100114-055104

Cited by 84 publications

(111 citation statements)

References 116 publications

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“…Such moderate divergence values, also observed (up to 14% genetic diversity) when including 30 HPgV genotypes 1 to 6 reference sequences, were considered as typical for members of this viral group . Thus, the observed genetic diversity among French genotype 2 isolates is consistent with well known aspects of pegiviruses natural history, that is, a very probable long‐term presence and coevolution of the virus with humans, combined with multiple routes of transmission, persistent asymptomatic infections, and high rates of mutation/replication …”

Section: Discussionsupporting

confidence: 77%

“…Human pegivirus (HPgV), formerly known as GBV‐C, is a member of the genus Pegivirus , family Flaviviridae, composed of isolates identified in various mammalian hosts . Recent taxonomic evolutions and proposals related to these single‐stranded RNA viruses allow the current description of 11 species within the genus Pegivirus ( Pegivirus A‐K ), the human and nonhuman primate pegivirus isolates being assigned to species Pegivirus C .…”

Section: Introductionmentioning

confidence: 99%

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Human pegivirus isolates characterized by deep sequencing from hepatitis C virus‐RNA and human immunodeficiency virus‐RNA–positive blood donations, France

Jordier

Deligny

Barre

et al. 2018

Journal of Medical Virology

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Human pegivirus (HPgV, formerly GBV-C) is a member of the genus Pegivirus, family Flaviviridae. Despite its identification more than 20 years ago, both natural history and distribution of this viral group in human hosts remain under exploration. Analysis of HPgV genomes characterized up to now points out the scarcity of French pegivirus sequences in databases. To bring new data regarding HPgV genomic diversity, we investigated 16 French isolates obtained from hepatitis C virus-RNA and human immunodeficiency virus-RNA-positive blood donations following deep sequencing and coupled molecular protocols. Initial phylogenetic analysis of 5'-untranslated region (5'-UTR)/E2 partial sequences permitted to assign HPgV isolates to genotypes 2 (n = 15) and 1 (n = 1), with up to 16% genetic diversity observed for both regions considered. Seven nearly full-length representative genomes were characterized subsequently, with complete polyprotein coding sequences exhibiting up to 13% genetic diversity; closest nucleotide (nt) divergence with available HPgV sequences was in the range 7% to 11%. A 36 nts deletion located on the NS4B coding region (N-terminal part, 12 amino acids) of the genotype 1 HPgV genome characterized was identified, along with single nucleotide deletions in two genotype 2, 5'-UTR sequences.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Human pegivirus isolates characterized by deep sequencing from hepatitis C virus‐RNA and human immunodeficiency virus‐RNA–positive blood donations, France

Jordier

Deligny

Barre

et al. 2018

Journal of Medical Virology

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“…Serum and liver samples from the deceased horse obtained postmortem and from the administered tetanus antitoxin tested negative for the 3 recently identified horse flaviviruses, NPHV, TDAV, and EPgV ( 29 ). We used an unbiased amplification and high-throughput sequencing approach to identify known and new viruses in the antitoxin and liver sample ( 19 , 23 , 30 ).…”

Section: Resultsmentioning

confidence: 99%

New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product

Divers¹,

Tennant²,

Kumar³

et al. 2018

Emerg. Infect. Dis.

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237

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Equine serum hepatitis (i.e., Theiler’s disease) is a serious and often life-threatening disease of unknown etiology that affects horses. A horse in Nebraska, USA, with serum hepatitis died 65 days after treatment with equine-origin tetanus antitoxin. We identified an unknown parvovirus in serum and liver of the dead horse and in the administered antitoxin. The equine parvovirus-hepatitis (EqPV-H) shares <50% protein identity with its phylogenetic relatives of the genus Copiparvovirus. Next, we experimentally infected 2 horses using a tetanus antitoxin contaminated with EqPV-H. Viremia developed, the horses seroconverted, and acute hepatitis developed that was confirmed by clinical, biochemical, and histopathologic testing. We also determined that EqPV-H is an endemic infection because, in a cohort of 100 clinically normal adult horses, 13 were viremic and 15 were seropositive. We identified a new virus associated with equine serum hepatitis and confirmed its pathogenicity and transmissibility through contaminated biological products.

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“…Recently, multiple novel animal hepaciviruses naturally infecting various species have been identified (9,10). Viruses classified within the genus Hepacivirus have been discovered in dogs (11) and subsequently in horses (12), rodents (13)(14)(15), bats (16), Old World primates (17), cattle (18), and recently catsharks (19).…”

mentioning

confidence: 99%

Immune protection against reinfection with nonprimate hepacivirus

Pfaender

Wälter

Grabski

et al. 2017

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

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Hepatitis C virus (HCV) displays a restricted host species tropism and only humans and chimpanzees are susceptible to infection. A robust immunocompetent animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control, and prophylactic vaccine development. The closest homolog of HCV is the equine nonprimate hepacivirus (NPHV), which shares similar features with HCV and thus represents an animal model to study hepacivirus infections in their natural hosts. We aimed to dissect equine immune responses after experimental NPHV infection and conducted challenge experiments to investigate immune protection against secondary NPHV infections. Horses were i.v. injected with NPHV containing plasma. Flow cytometric analysis was used to monitor immune cell frequencies and activation status. All infected horses became viremic after 1 or 2 wk and viremia could be detected in two horses for several weeks followed by a delayed seroconversion and viral clearance. Histopathological examinations of liver biopsies revealed mild, periportally accentuated infiltrations of lymphocytes, macrophages, and plasma cells with some horses displaying subclinical signs of hepatitis. Following viral challenge, an activation of equine immune responses was observed. Importantly, after a primary NPHV infection, horses were protected against rechallenge with the homologous as well as a distinct isolate with only minute amounts of circulating virus being detectable.hepatitis C virus | nonprimate hepacivirus | infection | immune protection | rechallenge H epatitis C virus (HCV) infections constitute a major global health problem with ∼130 million people being chronically infected (1). Once infected, 70-90% of individuals progress to chronicity, rendering HCV the leading cause of liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma (2). HCV is a blood-borne, positive-stranded RNA virus classified to the family of Flaviviridae within the genus Hepacivirus. Seven different HCV genotypes and numerous subtypes have been described, which differ on the nucleotide level by ∼30-35% between different genotypes and maximally 30% between subtypes (3). Furthermore, within infected individuals the virus circulates as a population of closely related but distinct genomes (4). Recently, significant progress has been made regarding the treatment of HCV with the implementation of direct-acting antiviral (DAA) drugs, which can be administered as all-oral IFN-free therapeutics and should help to reduce the global burden of HCV infections (5). However, there are still many caveats, including high treatment costs and the risk of reinfection after successful therapy, which is a problem especially in patient populations with frequent exposure to HCV. Furthermore, the inadequacy of current HCV screening programs often results in late diagnosis of chronic HCV infection and subsequent proceeding to end-stage liver diseases (6). All of these challenges highlight the necessity for a prophylactic vaccine against HCV, ...

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The Strange, Expanding World of Animal Hepaciviruses

Cited by 84 publications

References 116 publications

Human pegivirus isolates characterized by deep sequencing from hepatitis C virus‐RNA and human immunodeficiency virus‐RNA–positive blood donations, France

Human pegivirus isolates characterized by deep sequencing from hepatitis C virus‐RNA and human immunodeficiency virus‐RNA–positive blood donations, France

New Parvovirus Associated with Serum Hepatitis in Horses after Inoculation of Common Biological Product

Immune protection against reinfection with nonprimate hepacivirus

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