Microbiota may affect the tumor type but not overall tumor development in two models of heritable cancer.

Microbial impact on tumorigenesis of heritable cancers proximal to the gut is well documented. Whether the microbiota influences cancers arising from inborn mutations at sites distal to the gut is undetermined. Using two models of heritable cancer, we found the microbiota to be inconsequential for tumor development. However, the type of tumor that develops may be influenced by the microbiota. This work furthers our understanding of the microbial impact on tumor development.

A single dominant locus restricts retrovirus replication in YBR/Ei mice.

Differential responses to viral infections are influenced by the genetic makeup of the host. Studies of resistance to retroviruses in human populations are complicated due to the inability to conduct proof-of-principle studies. Inbred mouse lines, which have a range of susceptible phenotypes to retroviruses, are an ideal tool to identify and characterize mechanisms of resistance and define their genetic underpinnings. YBR/Ei mice become infected with Mouse Mammary Tumor Virus, a mucosally transmitted murine retrovirus, but eliminate the virus from their pedigrees. Virus elimination correlates with a lack of virus-specific neonatal oral tolerance, which is a major mechanism for blocking the anti-virus response in susceptible mice. Virus control is unrelated to virus-neutralizing antibodies, cytotoxic CD8+ T cells, NK cells, and NK T cells, which are the best characterized mechanisms of resistance to retroviruses. We identified a single, dominant locus that controls the resistance mechanism, which we provisionally named attenuation of virus titers (Avt) and mapped to the distal region of chromosome 18. IMPORTANCE Elucidation of the mechanism that mediates resistance to retroviruses is of fundamental importance to human health, as it will ultimately lead to knowledge of the genetic differences among individuals in susceptibility to microbial infections.

Retroviral Infection and Commensal Bacteria Dependently Alter the Metabolomic Profile in a Sterile Organ.

Both viruses and bacteria produce "pathogen associated molecular patterns" that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites, while viruses could change the metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of murine leukemia virus-infected mice monocolonized with Lactobacillus murinus to show that viral infection significantly changes the metabolite profile of monocolonized mice. We hypothesize that these changes could contribute to viral pathogenesis or to the host response against the virus and thus open a new avenue for future investigations.

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

Both viruses and bacteria produce 'pathogen associated molecular patterns' that may affect microbial pathogenesis and anti-microbial responses. Additionally, bacteria produce metabolites while viruses could change metabolic profiles of the infected cells. Here, we used an unbiased metabolomics approach to profile metabolites in spleens and blood of Murine Leukemia Virus-infected mice monocolonized with Lactobacillus murinus to show that viral infection significantly changes the metabolite profile of monocolonized mice. We hypothesize that these changes could contribute to viral pathogenesis or to the host response against the virus and thus, open a new avenue for future investigations.

Gut commensal bacteria enhance pathogenesis of a tumorigenic murine retrovirus.

The influence of the microbiota on viral transmission and replication is well appreciated. However, its impact on retroviral pathogenesis outside of transmission/replication control remains 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 is due to suppression of the adaptive immune response through upregulation of several negative regulators of immunity. These negative regulators include Serpinb9b and Rnf128, which are associated with a poor prognosis of some spontaneous human cancers. Upregulation of Serpinb9b is mediated by sensing of bacteria by the NOD1/NOD2/RIPK2 pathway. This work describes a mechanism by which the microbiota enhances tumorigenesis within gut-distant organs and points at potential targets for cancer therapy.