The Role of the Microbiota in Retroviral Pathogenesis

The influence of the microbiota on viral transmission and replication is well appreciated. However, its impact on retroviral pathogenesis outside of transmission/replication control remained unknown. Using Murine Leukemia Virus (MuLV), we found that some commensal bacteria promoted the development of leukemia induced by this retrovirus. The promotion of leukemia development by commensals was due to suppression of the adaptive immune response through upregulation of several negative regulators of immunity. These negative regulators included Serpinb9b and Rnf128, which are associated with a poor prognosis of some spontaneous human cancers. Upregulation of Serpinb9b was mediated by sensing of bacteria by NOD1/NOD2/RIPK2 pathway. Using an unbiased metabolomics approach, we also identified various metabolites whose presence and abundances in the periphery is mediated by both bacterial colonization and MuLV infection. Highlighting the potential for metabolites to also influence virally induced leukemia development. This work describes a novel mechanism by which the microbiota enhances tumorigenesis within gut-distant organs and points at potential new targets for cancer therapy.