Discovery of a circovirus involved in human hepatitis

Although transmission of animal viruses to humans is regularly reported in the scientific literature, detection of a new virus in a patient is rare in Europe. But in a new study, scientists and doctors have identified the first circovirus associated with hepatitis in humans. ” The patient had unprovoked chronic hepatitis, with few symptoms. He underwent a double heart and lung transplant
17 years ago, very regular monitoring. Over several years, we were able to access many samples, which allowed us to identify this new virus that was unexpected.
“, explains Marc Eloit, the last author of the study, head of the pathogen detection laboratory at the Pasteur Institute and professor of virology at the Alfort National Veterinary School (EnvA). His laboratory specializes in the search for pathogens in patients with suspected serious infections for which the cause cannot be determined.

As part of a collaboration with the Hôpital Necker – Enfants Malades AP-HP clinical microbiology department, pathological tissue samples were obtained from this 61-year-old patient who was receiving immunosuppressive therapy and had no identifiable cause of hepatitis in March 2022. by sequencing for microbial sequencing. The sequences of RNA (ribonucleic acid) extracted from these tissues were analyzed and compared with the sequences of already known microbes. ” It’s about identifying interesting sequences among all the sequences obtained, a needle in a haystack! “, researcher Marc Eloit emphasizes. Parallel analysis of these thousands of RNAs was possible thanks to the use of mNGS high-throughput sequencing methods (metagenomic Next generation sequencing) and powerful computer algorithms. After excluding common common etiologies, the analysis identified an as yet unknown type of circovirus and tentatively named it. Human circovirus 1 (HCirV-1). No other viral or bacterial sequences were found.

Later, the involvement of HCirV-1 in hepatitis was demonstrated in the context of the patient’s transplant, thanks to the analysis of samples taken in previous years for his follow-up. The results showed that the viral genome of HCirV-1 was not detected in blood samples from 2017 to 2019, after which its concentration reached a peak in September 2021. The virus was found to replicate in liver cells (2-3% of liver cells were infected), demonstrating the role of HCirV-1 in liver damage: indeed, this virus destroys the liver cell after using its resources to replicate.

Since November 2021, after antiviral treatment, the patient’s liver enzymes have returned to normal levels, indicating that liver cytolysis has stopped.

The diagnosis of undiagnosed hepatitis remains a major challenge, as evidenced by the WHO-reported cases of acute hepatitis in children in the UK and Ireland last April. ” It is important to know the cause of hepatitis, especially if it is viral, in order to tailor treatment and follow-up of patients. The identification of this novel pathogenic virus for humans and the development of a test that can be performed by any hospital laboratory provide a new tool for the diagnosis and monitoring of patients with hepatitis. “says Anne Jamet from the clinical microbiology department at Necker Hospital – Pediatric Patient AP-HP associated with Inserm and last author of the study.

Although some circoviruses are pathogenic for animals and can be vaccinated, especially in pigs, this is the first circovirus pathogenic for humans. The patient’s symptoms remained mild, and the identification of this virus was due to close follow-up due to his double transplant. The origin of the virus, the virus circulating in humans or the virus of animal origin, as well as the source of the infection itself (contact, food, etc.) are being determined. Thanks to this discovery, scientists were able to develop a specific PCR test available for the etiological diagnosis of hepatitis of unknown origin. A serological test is also prepared.

These results indicate the interest of this type of sequencing analysis to identify new or unexpected pathogens. It is always important for clinicians to know whether it is a viral infection in order to tailor treatment. It is also important to have the ability to identify a new pathogen and develop a diagnostic test when an infection is unexplained, as any new case of infection with a pathogen that originates in humans may signal the start of an epidemic. Mark Eloit concludes. This test, available in the medical community, is now available for other cases of unexplained hepatitis.

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