Oncoviruses and innate immunity

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Thèmes de recherche

Oncoviruses must have the capacity to escape immune surveillance and promote cellular transformation in order to persist and progress in humans. Innate immune responses play a crucial role in the control of viral replication and are required for a timely orchestration of specific adaptive responses against the infection. The innate immune system can sense pathogen components via the Toll Like Receptor (TLR) family and cytosolic receptors. The main objective of our team is to establish a causal role of infectious agents in human cancer and how they affect the innate immune response. We observed that the human papillomavirus type 16 (HPV16) (associated with cervical cancer), a virus that infects the basal epithelium, can effectively deregulate the expression and function of Toll Like Receptor 9 (TLR9) which can sense double-stranded DNA motifs. We will expand our research by elucidating how TLR9 is deregulated by hepatitis B and to examine other double-stranded DNA sensors such as the AIM2 inflammasome in the context of oncoviral infection. Another ambitious goal will be to determine whether TLR9 has a role in regulating the cell cycle, in particular, to determine the mechanisms that induce events leading to cell death. This highlights a new function of Toll Like Receptors and underscores why TLR9 is targeted by oncoviruses. All studies are conducted in humans and require intensive use of primary human cell cultures and our data will be corroborated in cohorts of normal and cancerous tissues. In addition, in collaboration with the International Agency for Research on Cancer, we seek to examine whether certain polymorphisms in innate receptors will influence the risk of cervical cancer among women in different regions of the world, including France.

Principales découvertes

  • Identification of a novel mechanism by which TLR9 expression is blocked by HPV16, EBV and HBV (2010-ongoing)
  • Gene signature by TLR9 induction of cell death (2012- ongoing)
  • HBV suppression of AIM2 responses in the human liver (2012-ongoing)

Sponsors

INSERM, EMBO, University Lyon I, L’ANRs, La Ligue Contre le Cancer, CLARA, L’ARC