Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus

Abstract

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. 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.

Retroviral infection and commensal bacteria dependently alter the metabolomic profile in a sterile organ

“…While the effect of commensal microbe-derived metabolites on cellular activities and pathogen infections is clear, a reciprocal impact of the commensal microbiota and viral pathogens on metabolites has yet to be investigated. We previously showed commensal bacteria Lactobacillus murinus promotes the pathogenesis of murine retrovirus Murine Leukemia Virus (MuLV) (19). We used a similar model coupled with an unbiased metabolomics approach to investigate the influence of cross-talk between commensal bacteria and viral infection on metabolites.…”