Project Funding Details

Chronic inflammation is a major risk factor for the development of cancer. In some specific cancers, such as gastric cancer and hepatocellular carcinoma, predisposing chronic inflammation has been linked to persistent infection with specific pathogens. Colorectal cancer has a particularly strong inflammatory basis, demonstrated by studies showing that anti-inflammatory drugs significantly reduce cancer risk, but the contribution of infection with enteric viruses to colorectal cancer has not been studied. Human noroviruses are a leading cause of gastrointestinal (GI) infections worldwide but only recently has it been appreciated that these viruses may persist beyond the resolution of GI symptoms. In fact, norovirus infection has been demonstrated to have a prevelance as high as 13% in asymptomatic individuals. The closely related mouse model pathogen, murine norovirus (MNV) is a mouse model of persistent viral infection in the gastro-intestinal tract. Additionally, in vitro studies have shown that detection of MNV through molecular sensors triggers the production of inflammatory cytokines with a demonstrated role in tumor promotion. Therefore, MNV is a good model to assess the contribution of persistent viral infection in the GI tract to the development of colorectal cancer. This proposal will be define the impact of persistent MNV infection on resident cells and inflammatory cytokines in the gut. An established mouse model of colorectal cancer will be used to assess the contribution of persistent MNV infection to colorectal cancer development and the role of inflammatory cytokines in this process. A linkage between inflammation and cancer in this model system will demonstrate that enteric viruses can be a risk factor for colorectal cancer development, and identification of specific pathways at play will suggest approaches for treatment and prevention.

Chronic inflammation is a major risk factor for the development of cancer. In some specific cancers, such as gastric cancer and hepatocellular carcinoma, predisposing chronic inflammation has been linked to persistent infection with specific pathogens. Colorectal cancer has a particularly strong inflammatory basis, demonstrated by studies showing that anti-inflammatory drugs significantly reduce cancer risk, but the contribution of infection with enteric viruses to colorectal cancer has not been studied. Human noroviruses are a leading cause of gastrointestinal (GI) infections worldwide but only recently has it been appreciated that these viruses may persist beyond the resolution of GI symptoms. In fact, norovirus infection has been demonstrated to have a prevelance as high as 13% in asymptomatic individuals. The closely related mouse model pathogen, murine norovirus (MNV) is a mouse model of persistent viral infection in the gastro-intestinal tract. Additionally, in vitro studies have shown that detection of MNV through molecular sensors triggers the production of inflammatory cytokines with a demonstrated role in tumor promotion. Therefore, MNV is a good model to assess the contribution of persistent viral infection in the GI tract to the development of colorectal cancer. This proposal will be define the impact of persistent MNV infection on resident cells and inflammatory cytokines in the gut. An established mouse model of colorectal cancer will be used to assess the contribution of persistent MNV infection to colorectal cancer development and the role of inflammatory cytokines in this process. A linkage between inflammation and cancer in this model system will demonstrate that enteric viruses can be a risk factor for colorectal cancer development, and identification of specific pathways at play will suggest approaches for treatment and prevention.