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PLoS pathogens2020; 16(7); e1008677; doi: 10.1371/journal.ppat.1008677

Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis.

Abstract: Pegiviruses frequently cause persistent infection (as defined by >6 months), but unlike most other Flaviviridae members, no apparent clinical disease. Human pegivirus (HPgV, previously GBV-C) is detectable in 1-4% of healthy individuals and another 5-13% are seropositive. Some evidence for infection of bone marrow and spleen exists. Equine pegivirus 1 (EPgV-1) is not linked to disease, whereas another pegivirus, Theiler's disease-associated virus (TDAV), was identified in an outbreak of acute serum hepatitis (Theiler's disease) in horses. Although no subsequent reports link TDAV to disease, any association with hepatitis has not been formally examined. Here, we characterized EPgV-1 and TDAV tropism, sequence diversity, persistence and association with liver disease in horses. Among more than 20 tissue types, we consistently detected high viral loads only in serum, bone marrow and spleen, and viral RNA replication was consistently identified in bone marrow. PBMCs and lymph nodes, but not liver, were sporadically positive. To exclude potential effects of co-infecting agents in experimental infections, we constructed full-length consensus cDNA clones; this was enabled by determination of the complete viral genomes, including a novel TDAV 3' terminus. Clone derived RNA transcripts were used for direct intrasplenic inoculation of healthy horses. This led to productive infection detectable from week 2-3 and persisting beyond the 28 weeks of study. We did not observe any clinical signs of illness or elevation of circulating liver enzymes. The polyprotein consensus sequences did not change, suggesting that both clones were fully functional. To our knowledge, this is the first successful extrahepatic viral RNA launch and the first robust reverse genetics system for a pegivirus. In conclusion, equine pegiviruses are bone marrow tropic, cause persistent infection in horses, and are not associated with hepatitis. Based on these findings, it may be appropriate to rename the group of TDAV and related viruses as EPgV-2.
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Publication Date: 2020-07-10 PubMed ID: 32649726PubMed Central: PMC7375656DOI: 10.1371/journal.ppat.1008677Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

Equine pegiviruses, a type of virus that often result in long-lasting infections, live in the bone marrow and are not linked to causing liver diseases.

Background

  • The article begins by giving an overview of pegiviruses. They often cause long-lasting infections, lasting over six months, but they do not typically link with any noticeable disease symptoms.
  • Human pegivirus can be detected in about 1-4% of healthy individuals, and about 5-13% of people have a positive antibody reaction to the virus, indicating previous exposure.
  • There is some evidence of the virus infecting the bone marrow and spleen. Equine (horse) pegivirus 1 (EPgV-1) is not associated with any known diseases. Another type of pegivirus, Theiler’s disease-associated virus (TDAV), was found in an outbreak of acute serum hepatitis (otherwise known as Theiler’s disease) in horses, but no further link to the disease has been reported.

Goals of the Research

  • The purpose of this study was to describe the movement within the host, sequence diversity, persistence, and potential link to liver disease in horses for EPgV-1 and TDAV.

      • Key Findings

      • An analysis of several tissue types showed high virus counts only in serum (animal fluid), bone marrow, and spleen. The virus was found to reproduce in bone marrow, lymph nodes, and blood cells. However, it was found sporadically in the liver.
      • To eliminate the impact of pre-existing infections, the researchers built full-length cDNA clones. This was possible through the entire genome definition, which includes a novel TDAV 3′ terminus identified. The RNA transcripts derived from these clones were administered directly to healthy horses, leading to a successful infection detectable from the 2nd or 3rd weeks and persisting beyond 28 weeks.
      • No signs of illness or increased liver enzymes were observed, indicating that these two viruses, despite their long-term presence in the horses, do not lead to clinical disease or liver damage. Importantly, the viral sequences also did not change, suggesting the viruses were active.
      • This study is the first to successfully initiate a viral RNA outside the liver (extrahepatic launch) and to establish a robust reverse genetics system—reconstructing and modifying the virus—for a pegivirus.

      Conclusion

      • The researchers concluded that equine pegiviruses are typically found in the bone marrow, cause long-lasting infections in horses, but do not cause liver diseases.
      • In light of these findings, they suggested renaming the group of TDAV and similar viruses to EPgV-2, essentially classifying them as another variant of equine pegiviruses.

Cite This Article

APA
Tomlinson JE, Wolfisberg R, Fahnøe U, Sharma H, Renshaw RW, Nielsen L, Nishiuchi E, Holm C, Dubovi E, Rosenberg BR, Tennant BC, Bukh J, Kapoor A, Divers TJ, Rice CM, Van de Walle GR, Scheel TKH. (2020). Equine pegiviruses cause persistent infection of bone marrow and are not associated with hepatitis. PLoS Pathog, 16(7), e1008677. https://doi.org/10.1371/journal.ppat.1008677

Publication

PLoS pathogens
ISSN: 1553-7374
NlmUniqueID: 101238921
Country: United States
Language: English
Volume: 16
Issue: 7
Pages: e1008677

Researcher Affiliations

Tomlinson, Joy E
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Wolfisberg, Raphael
  • Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Fahnøe, Ulrik
  • Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Sharma, Himanshu
  • Center for Vaccines and Immunity, Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
Renshaw, Randall W
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Nielsen, Louise
  • Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Nishiuchi, Eiko
  • Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Holm, Christina
  • Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Dubovi, Edward
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Rosenberg, Brad R
  • Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Tennant, Bud C
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Bukh, Jens
  • Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
Kapoor, Amit
  • Center for Vaccines and Immunity, Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States of America.
Divers, Thomas J
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Rice, Charles M
  • Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.
Van de Walle, Gerlinde R
  • Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Scheel, Troels K H
  • Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Hvidovre Hospital and Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
  • Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, New York, United States of America.

MeSH Terms

  • Animals
  • Bone Marrow / virology
  • Flaviviridae
  • Flavivirus Infections / veterinary
  • Flavivirus Infections / virology
  • Hepatitis, Viral, Animal / virology
  • Horse Diseases / virology
  • Horses

Grant Funding

  • K08 AI141767 / NIAID NIH HHS

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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