Discovery of a hitherto unknown virus affecting the liver

Discovery of a hitherto unknown virus affecting the liver

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    A still unknown species of circovirus was recently identified by French researchers, in a woman with signs of liver disease. This is the first circovirus linked to hepatitis in humans.

    It is rare for a new virus affecting humans to be discovered in Europe. Yet this is what has happened in France in recent months, according to a press release and a noticeable publication in the review Emerging infectious Disease.

    Scientists from the Institut Pasteur, the Necker-Enfants Malades Hospital AP-HP, Inserm within the Imagine Institute, Paris Cité University and the National Veterinary School of Alfort (EnvA) , have identified a yet unknown species of circovirus, tentatively named Human Circovirus 1 (HCirV-1). As the Institut Pasteur website indicates, this family of very resistant small DNA viruses was initially identified in 1974 in different animal species, but HCirV-1 is a new virus, distant from known animal circoviruses and the first linked to hepatitis.

    A heart and lung transplant patient 17 years earlier

    According to the publication, the research focused on a 61-year-old patient on immunosuppressive therapy and suffering from unexplained hepatitis, with few symptoms. “She had received a double heart and lung transplant 17 years earlier, with very regular follow-up. We were able to access many samples over several years, which allowed us to identify this new virus, which was unexpected to say the least.”, explains Marc Eloit, author and head of the Pathogen Discovery laboratory at the Institut Pasteur and Professor of Virology at the National Veterinary School of Alfort (EnvA). The scientist is precisely specialized in this search for pathogens in patients whose causes are not identifiable.

    A French collaboration between several research centers

    As part of a collaboration with the clinical microbiology department of the Necker-Enfants Malades Hospital AP-HP, the pathological tissue samples from this patient were sequencing for microbial sequences. Through the use of high-throughput mNGS sequencing techniques (metagenomic Next Generation Sequencing) and powerful computer algorithms, the sequences of thousands of RNAs (Ribonucleic acid) extracted from these tissues were analyzed and compared to those of already known microbes.

    After ruling out common common etiologies, the analysis identified a yet unknown species of circovirus, tentatively named Human circovirus 1 (HCirV-1). No other viral or bacterial sequences were found, thus making an unprecedented discovery.

    A virus disappeared after treatment

    The involvement of HCirV-1 in hepatitis was then demonstrated thanks to the analysis of samples from the patient taken during previous years for her follow-up in the context of her transplants.

    • The HCirV-1 viral genome was undetectable in blood samples from 2017 to 2019;
    • Its concentration peaked in September 2021 and multiplication of the virus in liver cells was revealed (2-3% of liver cells were infected), demonstrating the role of HCirV-1 in liver damage;
    • From November 2021, after antiviral treatment, liver enzymes returned to a normal level in the patient, indicating a cessation of hepatic cytolysis.

    Should we fear this new virus?

    If the word virus can give cold sweats at its mere mention, the discovery of this hepatic virus, made possible by monitoring the patient, is nevertheless a breakthrough in the world of medicine. Contacted by Doctissimo, Professor Eloit explains to us how this virus search procedure works in France, regularly carried out in certain types of patients:

    “It is a collaboration set up with the Necker hospital and most French hospitals which means that seriously ill patients with suspicion of an undiagnosed infectious disease will benefit from the tools put in place by the Institut Pasteur. There is thus a double association between better management of the disease and interest in research; it is in this context that this patient was taken care of and that the samples were taken”.

    As for the fear of seeing a new virus impact France that readers may fear, the scientist recalls that the concern is not justified at this stage: “When we are in the presence of an unknown virus, we must always ask ourselves if we are in the presence of something completely new in an emerging situation, in which case it would be the first case, or the new demonstration of a virus that has been around for a long time but had not been detected. Testing is ongoing.”

    Why is this discovery important?

    But thanks to this discovery, research is advancing: scientists have been able to develop a specific PCR test now available for the etiological diagnosis of hepatitis of unknown origin, already requested in several hospitals to evaluate cases of undiagnosed hepatitis. A serological test is also in development.

    These results show the interest of this type of analysis by sequencing to identify new or unexpected pathogens. It is always important for clinicians to know whether it is a viral infection or not, in order to adapt treatment. It is also essential to have the ability to identify a new pathogen when an infection is unexplained and to develop a diagnostic test, as potentially any new case of infection with an emerging pathogen in humans may witness the beginning of an epidemic”, concludes Marc Eloit.

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