Vivien Béziat

Mucocutaneous oncoviruses are DNA viruses that can cause epithelial tumors. Three viruses are currently recognized as mucocutaneous oncogenic viruses in humans: Kaposi’s sarcoma-associated herpes virus (KSHV, also known as HHV8), human papillomaviruses (HPV), and Merkel polyomavirus (MCPyV). Clinical phenotypes resulting from infection with these oncoviruses range from asymptomatic infection to invasive cancers. For example, HPV-induced anogenital cancers remain a leading cause of death in women worldwide. Patients with inherited immune deficiencies are prone to the development of infectious diseases caused by a narrow or broad spectrum of pathogens, including oncoviruses in some cases. 

The team works around two main research axes:

1. Genetics of immunity to mucocutaneous oncoviruses. Through a national and global network of collaborators, we recruit patients with Kaposi’s sarcoma, severe mucocutaneous warts, Buschke-Löwenstein tumors or “tree man” syndrome, two devastating benign tumors caused by HPV6 and HPV2 respectively. Using high-throughput sequencing (whole exome or whole genome sequencing) and population genetics, we are searching for genetic variations that may be the cause of these diseases. Candidate variations are validated using experimental approaches of molecular biology, biochemistry, immunology and virology. Recently, our team has reported CARMIL2 deficiency in patients with combined immune deficiency and recalcitrant warts, and CD28 deficiency in patients with recalcitrant warts, including a patient with “tree man” syndrome.
2. Study of the in situ immune response against HPV using different models of inherited immune deficiency. Although HPV is a long known human pathogen, the immune response against it remains very poorly characterized, in particular because of difficulty in accessing regressed wart samples, and because the majority of studies are performed from blood, whereas infection takes place in tissues. In order to overcome this lack of knowledge, which hinders our understanding of the disease of the patients studied by the team, we use state-of-the-art technologies such as mass cytometry, mass cytometry imaging (MCI) coupled with analytical approaches based on artificial intelligence, or different single-cell RNA sequencing approaches from blood or skin samples (scRNAseq). Coupled with unique access to human models of viral regression or persistence, these new technologies allow us to study with an unprecedented level of precision the immune response against HPV in the skin. 

Overall, our work aims to provide a better understanding of mucocutaneous immunity to oncoviruses, in its leukocyte and non-leukocyte components. In the longer term, our ambition is to apply the acquired knowledge to improve the management of mucocutaneous pathologies.