Mallika Dureja
Scientists from the Institut Pasteur, Necker-Enfants Malades Hospital (AP-HP), Inserm in the Imagine Institute, Université Paris Cite, and the Alfort National Veterinary School (EnvA) have identified a previously unknown species of circovirus, tentatively dubbed human circovirus 1. (HCirV-1).
Circoviruses are a family of small, highly resistant DNA viruses first identified in 1974 in a variety of animal species, where they can cause respiratory, renal, dermatological, and reproductive issues. HCirV-1 is a novel virus that is unrelated to previously identified animal circoviruses. It was shown to be responsible for liver injury in a patient receiving immunosuppressive therapy. This hepatitis-related discovery of the first human circovirus was published in the journal Emerging Infectious Diseases on January 3, 2023.
Also read: Putin gave Biden $12,000 pen set months before Ukraine invasion
Although the transmission of animal viruses to humans is frequently reported in scientific literature, it is uncommon for a patient in Europe to be diagnosed with a novel virus. Scientists and clinicians have identified the first circovirus associated with human hepatitis as part of a recent study. “The patient exhibited few symptoms of inexplicable chronic hepatitis. She had received a heart-lung transplant seventeen years ago and has been routinely monitored since. We had access to a large number of samples over a number of years and were therefore able to identify this unexpectedly novel virus “explains Marc Eloit, the study’s last author, Head of the Pathogen Discovery laboratory at Institut Pasteur, and Professor of Virology at the Alfort National Veterinary School (EnvA). His laboratory specialises in identifying pathogens in patients suspected of suffering from a severe infection of unknown origin.
In March 2022, in collaboration with the Department of Clinical Microbiology at Necker-Enfants Malades Hospital (AP-HP), the pathological tissue samples of this immunosuppressed 61-year-old female patient whose hepatitis had no identifiable cause were sequenced in search of microbial sequences. The extracted RNA (ribonucleic acid) sequences from the tissues were analysed and compared to those of known microorganisms. Scientist Marc Eloit continues, “The goal is to identify sequences of relevance among all the sequences obtained, which is like looking for a needle in a haystack.” These thousands of RNA sequences were analysed in parallel using high-throughput sequencing techniques and complex algorithms. After ruling out prevalent causes, the analysis led to the identification of a previously unknown species of circovirus, tentatively dubbed human circovirus 1 (HCirV-1). There was no additional viral or bacterial sequence found.
The involvement of HCirV-1 in the hepatitis was then demonstrated by analysing patient samples collected in previous years as part of her post-transplant therapy. The results revealed that the HCirV-1 viral genome was undetectable in blood samples between 2017 and 2019, and that its concentration peaked in September 2021. Viral replication in liver cells was demonstrated (2 to 3% of liver cells were infected), indicating the role of HCirV-1 in liver damage: once the virus has exhausted the liver cell’s resources to replicate, it destroys the cell.
The patient’s liver enzymes returned to normal levels in November 2021, indicating the end of hepatic cytolysis, as a result of antiviral treatment.
As evidenced by the cases of acute hepatitis documented in children in the United Kingdom and Ireland last April and reported by WHO, diagnosing hepatitis of unknown aetiology continues to be a significant challenge. “In order to effectively treat and monitor patients, we must determine the cause of the hepatitis, and in particular whether it is viral. The discovery of this novel human-pathogenic virus and the development of a test that can be performed in any hospital laboratory provide a new diagnostic and monitoring tool for hepatitis patients “Anne Jamet of the Department of Clinical Microbiology at Necker-Enfants Malades Hospital (AP-HP), who is also affiliated with Inserm and the study’s co-last author, emphasises the need for further research into the topic.
Although some circoviruses are pathogenic for animals and vaccines can be administered, particularly in piglets, this is the first known human-pathogenic circovirus. The patient’s symptoms remained moderate; the virus was identified because she was closely monitored after undergoing a combined transplant. The origin of the virus — whether it is circulating among humans or animals — has yet to be determined, and the source of infection (contact, food, etc.) is uncertain. In response to their discovery, scientists have created a specific PCR test for etiological diagnosis of hepatitis of unknown origin. Also being developed is a serological test.
“These findings demonstrate the usefulness of this form of sequencing analysis for identifying novel or unexpected pathogens. It is always essential for clinicians to determine whether or not an infection is viral in order to tailor treatment accordingly. Additionally, it is crucial to be able to identify a novel pathogen when an infection remains unexplained and to develop a diagnostic test, as any new case of human infection with an emerging pathogen may herald the beginning of an outbreak “concludes Marc Eloit. Other cases of unexplained hepatitis can now be conducted with relative ease thanks to the test’s availability to the medical community.
