Scientists have identified a previously unknown species of circovirus, tentatively named human circovirus 1 (HCirV-1). The research was carried out by scientists from Institut Pasteur, Necker-Enfants Malades Hospital (AP-HP), Inserm v Imagine Institute, Universite Paris Cite and Alfort National Veterinary School (EnvA).
Animal circoviruses
Circoviruses are a family of small, highly resistant DNA viruses that were originally identified in 1974 in various animal species, where they can cause respiratory, renal, dermatological and reproductive problems. HCirV-1 is a new virus that is distant from known animal circoviruses. It has been shown to be involved in liver damage in a patient undergoing immunosuppressive therapy. This discovery of the first hepatitis-associated circovirus in humans was published in the journal Emerging Infectious Diseases on January 3, 2023.
Although the transmission of animal viruses to humans is regularly reported in the scientific literature, it is rare for a new virus to be identified in a patient in Europe. However, in a recent study, scientists and doctors have identified the first circovirus involved in human hepatitis.
Marc Eloit, the last author of the study, head of the Institut Pasteur’s Pathogen Discovery laboratory. Professor of Virology at the Alfort National Veterinary School (EnvA). His laboratory specializes in pathogen identification in patients with suspected severe infection of unknown cause. He explains “The patient had unexplained chronic hepatitis with several symptoms. She underwent a heart and lung transplant 17 years ago and has been monitored regularly since then. Over several years, we had access to a large number of samples and were therefore able to identify this new virus, which was completely unexpected”.
In March 2022, in collaboration with the Department of Clinical Microbiology of the Hospital Necker-Enfants Malades (AP-HP), pathological tissue samples from this 61-year-old patient who was receiving immunosuppressive therapy and whose hepatitis had no identifiable cause were sequenced. to search for microbial sequences.
The RNA (ribonucleic acid) sequences extracted from the tissues were analyzed and compared to those of known microbes. “The goal is to identify the desired sequences among all the obtained sequences, which is like looking for a needle in a haystack!” continues scientist Marc Eloit. These thousands of RNA sequences were analyzed in parallel using high-throughput sequencing techniques and sophisticated mNGS (metagenomic next-generation sequencing) algorithms. After ruling out common etiologies, the analysis led to the identification of a previously unknown species of circovirus, provisionally named human circovirus 1 (HCirV-1). No other viral or bacterial sequences were found.
Replication of virus in liver cells
The involvement of HCirV-1 in hepatitis was then proven by analyzing samples taken from the patient in previous years as part of her post-transplantation treatment. The results showed that the HCirV-1 viral genome was undetectable in blood samples from 2017 to 2019, and then its concentration peaked in September 2021.
Replication of the virus in liver cells was demonstrated (2 to 3 percent of liver cells were infected), pointing to a role HCirV-1 in liver damage: once the virus uses the resources in the liver cell to replicate, it destroys the cell.
As of November 2021, after antiviral treatment, the patient’s liver enzymes returned to normal values, indicating the end of liver cytolysis. The diagnosis of hepatitis of unknown etiology remains a major challenge, as demonstrated by cases of acute hepatitis reported in children in the UK and Ireland last April and flagged by the WHO.
“We need to know the cause of hepatitis, and especially whether it is viral or not, so that we can offer appropriate treatment and monitor patients effectively. The identification of this new human-pathogenic virus and the development of a test that can be performed by any hospital laboratory offers a new tool for the diagnosis and monitoring of patients with hepatitis,” points out Anne Jamet from the Department of Clinical Microbiology at the Hospital Necker-Enfants Malades (AP-HP ), who is also associated with Inserm and co-authored the study.
Origin of the virus
Although some circoviruses are pathogenic to animals and can be given vaccines, especially in pigs, this is the first known circovirus to be pathogenic to humans. The patient’s symptoms remained mild; the virus was identified because she was closely monitored after the combined transplant.
The origin of the virus – whether it is circulating in humans or of animal origin – has not yet been identified and the source of infection (contact, food, etc.) remains unknown. After their discovery, scientists developed a specific PCR test that is now available for the etiological diagnosis of hepatitis of unknown origin. A serological test is also being developed.
“These results demonstrate the value of this type of sequencing analysis in identifying new or unexpected pathogens. It is always important for clinicians to know whether the infection is viral or not so that they can adjust treatment accordingly. It is also important that we are able to identify a new pathogen when an infection remains unexplained and develop a diagnostic test, as any new case of human infection with a new pathogen can potentially signal the beginning of an outbreak,” concludes Marc Eloit. The test is available to the medical community and can now be easily performed in other cases of unexplained hepatitis.
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