Human genetic determinants of leukocyte immunity to muco-cutaneous oncoviruses

Muco-cutaneous oncoviruses are DNA viruses that can cause epithelial tumors. Three such viruses are currently known in humans: Kaposi sarcoma-associated herpesvirus (KSHV, also known as HHV8), human papillomaviruses (HPVs), and Merkel cell polyomavirus (MCPyV). The clinical phenotypes resulting from infection with these oncoviruses range from asymptomatic infection to invasive cancers. Despite available vaccines, anogenital cancers induced by HPVs remain a leading cause of death in women worldwide.


My team aims to understand the pathogenesis of oncogenic virus-driven phenotypes via the discovery and exploration of monogenic inborn errors of immunity (IEI) . In particular, we study the human genetic determinants of leukocytic immunity against muco-cutaneous oncoviruses. Thanks to an international network of collaborators, we have recruited patients with Kaposi sarcoma, Merkel carcinoma, severe muco-cutaneous warts, Buschke-Löwenstein tumors, and the “Tree man” syndrome.


Using next generation sequencing (whole exome or whole genome sequencing, RNAseq), we search for candidate variants underlying these diseases. Candidate variants are tested using experimental approaches. We also use a number of cutting-edge technologies, such as mass cytometry, imaging mass cytometry (IMC) couple to artificial intelligence-based analytical approaches, or single cell RNA sequencing.

Recently, our team has identified CARMIL2 or CD28 deficiency in patients with severe HPV infection, or “Tree man” syndrome.


Imaging mass cytometry (IMC) data of a Buschke-Löwenstein tumor

Key references: 1. Béziat V@, Rapaport F, Hu J, Titeux M, Bonnet des Claustres M, Bourgey M, Griffin H, Bandet É, Ma CS, Sherkat R, Rokni-Zadeh H, Louis DM, Changi-Ashtiani M, Delmonte OM, Fukushima T, Habib T, Guennoun A, Khan T, Bender N, Rahman M, About F, Yang R, Rao G, Rouzaud C, Li J, Shearer D, Balogh K, Al Ali F, Ata M, Dabiri S, Momenilandi M, Nammour J, Alyanakian M-A, Leruez-Ville M, Guenat D, Materna M, Marcot L, Vladikine N, Soret C, Vahidnezhad H, Youssefian L, Saeidian AH, Uitto J, Catherinot É, Navabi SS, Zarhrate M, Woodley DT, Jeljeli M, Abraham T, Belkaya S, Lorenzo L, Rosain J, Bayat M, Lanternier F, Lortholary O, Zakavi F, Gros P, Orth G, Abel L, Prétet J-L, Fraitag S, Jouanguy E, Davis MM, Tangye SG, Notarangelo LD, Marr N, Waterboer T, Langlais D, Doorbar J, Hovnanian A, Christensen N, Bossuyt X, Shahrooei M, Casanova J-L. Humans with inherited T cell CD28 deficiency are susceptible to skin papillomaviruses but are otherwise healthy. Cell. 2021 Jul 8;184(14):3812-3828.e30. DOI: 10.1016/j.cell.2021.06.004.

2. Wang Y, Ma CS, Ling Y, Bousfiha A, Camcioglu Y, Jacquot S, Payne K, Crestani E, Roncagalli R, Belkadi A, Kerner G, Lorenzo L, Deswarte C, Chrabieh M, Patin E, Vincent QB, Müller-Fleckenstein I, Fleckenstein B, Ailal F, Quintana-Murci L, Fraitag S, Alyanakian M-A, Leruez-Ville M, Picard C, Puel A, Bustamante J, Boisson-Dupuis S, Malissen M, Malissen B, Abel L, Hovnanian A, Notarangelo LD, Jouanguy E#, Tangye SG#, Béziat V@,#, Casanova J-L#. Dual T cell– and B cell–intrinsic deficiency in humans with biallelic RLTPR mutations. J Exp Med. 2016 Oct 17;213(11):2413–2435. DOI: 10.1084/jem.20160576.

3. Béziat V@, Casanova J-L, Jouanguy E. Human genetic and immunological dissection of papillomavirus-driven diseases: new insights into their pathogenesis. Curr Opin Virol. 2021 Dec 1;51:9–15. DOI: 10.1016/j.coviro.2021.09.002




Team members

  • Vivien Béziat, PhD, Theme leader
  • Romain Lévy, MD-PhD
  • Anaïs Pereira, Research engineer
  • Marie Materna, PhD student
  • Mana Momenilandi, PhD student
  • Antoine Fayand, MD
  • Corentin Le Floch’, Master student