Document text
Principal Investigator: Jasmine Wright
Organization: WASHINGTON UNIVERSITY
Fiscal Year: 2024
Award: $35,482
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary/Abstract
Obesity is a global health concern as it is a risk factor for several of the leading causes of death such as heart
disease, kidney disease, and type 2 diabetes. Obesity drives dysregulated inflammation, which has been
shown to be a risk factor for increased morbidity and mortality in certain pulmonary viral infections such as
influenza A and SARS-CoV-2. Yet it is unknown how diet induced obesity (DIO)-associated inflammation
impacts the immune response to viruses that infect the gastrointestinal tract. It has been well-established that
DIO drives dynamic changes in intestinal immunity, including alterations in interferon gamma and IgA
production. Specifically, DIO induces skewing towards type I immunity, which is protective against intracellular
pathogens like viruses. Norovirus (NV) is one of the most prevalent gut viruses, as it is the number one cause
of acute viral gastroenteritis worldwide. However, the effects of DIO induced type 1, or anti-viral, skewing on
immunity to NV have yet to be elucidated.
My new preliminary data indicate that mice placed on a high fat diet (HFD) prior to infection with persistent
murine NV (MNV) strain CR6 clear the infection in just 28 days, while mice fed normal chow (NC) remain
persistently infected. This clearance appears to be independent of MNV receptor expression and viral tropism.
Additionally, we found that obese patients with symptoms of gastroenteritis are less likely to test positive for NV
than symptomatic lean controls, which further supports our mouse model indicating a HFD is protective against
NV infection in both mice and humans. We also observe changes in the humoral response to MNV in our
mouse model, as HFD-fed mice have an increase in serum MNV specific IgG and decrease in both serum and
secretory MNV specific IgA in comparison to infected mice on NC. These findings lead to my central
hypothesis that obesity drives alterations in intestinal immunity that promote an anti-viral state and
protect against norovirus infection. I have proposed two aims to address this hypothesis. In Aim 1, I will
elucidate the role of DIO-mediated changes in B and T cell responses in protection against MNV infection. In
Aim 2, I will determine the role of interferon signaling in DIO-associated clearance of MNV. This novel work will
advance our understanding of the relationship between diet and immunity to NV infection. This work also has
translational potential as it may provide insight to treatment for NV, as there is currently no vaccine for this
common virus.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><7S Gamma Globulin><Ab response><Acute><Address><Adoptive Transfer><Adult><Adult Human><Adult-Onset Diabetes Mellitus><Affect><Alimentary Canal><Antibodies><Antibody Formation><Antibody Production><B blood cells><B cell><B cells><B-Cells><B-Lymphocytes><B-cell><BMI><BMI percentile><BMI z-score><Blood Serum><Body mass index><Bp35><CD20><CD4 Cells><CD4 Positive T Lymphocytes><CD4 T cells><CD4 helper T cell><CD4 lymphocyte><CD4+ T-Lymphocyte><CD4-Positive Lymphocytes><CD8><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CD8B><CD8B1><CD8B1 gene><COVID-19 infection><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><Cardiac Diseases><Cardiac Disorders><Cause of Death><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Clinical Data><CoV-2><CoV2><Colon><Data><Diagnosis><Diet><Digestive Tract><Exhibits><Feces><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><GI Tract><Gastroenteritis><Gastrointestinal Tract><Gastrointestinal tract structure><Genes><Grippe><Heart Diseases><High Fat Diet><Host Defense Mechanism><Human><IFN><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><IgA><IgG><Immune><Immune Interferon><Immune response><Immune system><Immunes><Immunity><Immunoglobulin A><Immunoglobulin G><Immunological response><Impairment><Individual><Infection><Inflammation><Inflammatory><Influenza><Influenza A><Influenza A virus><Influenza Viruses Type A><Influenzavirus A><Interferon Gamma><Interferon Receptor><Interferon Type II><Interferons><Intestinal><Intestines><Intracellular Communication and Signaling><Ketosis-Resistant Diabetes Mellitus><Kidney Diseases><LYT3><Lamina Propria><Lead><Leanness><Leu-16><Lung><Lung Respiratory System><MS4A1><MS4A1 gene><MS4A2><Maturity-Onset Diabetes Mellitus><Measures><Mediating><Metabolic Diseases><Metabolic Disorder><Mice><Mice Mammals><Modern Man><Morbid Obesity><Morbidity><Morbidity - disease rate><Murine><Mus><NIDDM><Nephropathy><Non-Insulin Dependent Diabetes><Non-Insulin-Dependent Diabetes Mellitus><Noninsulin Dependent Diabetes><Noninsulin Dependent Diabetes Mellitus><Norovirus><Norwalk-like Viruses><Obese Mice><Obesity><Orthomyxovirus Type A><Pathogenesis><Pathway interactions><Pb element><Population><Predisposition><Production><Quetelet index><Regulation><Renal Disease><Risk Factors><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Serum><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Severe obesity><Severity of illness><Shapes><Signal Transduction><Signal Transduction Systems><Signaling><Slow-Onset Diabetes Mellitus><Stable Diabetes Mellitus><Susceptibility><Symptoms><T cell response><T2 DM><T2D><T2DM><T4 Cells><T4 Lymphocytes><T8 Cells><T8 Lymphocytes><Testing><Thesaurismosis><Thinness><Time><Tropism><Type 2 Diabetes Mellitus><Type 2 diabetes><Type A Influenza><Type II Diabetes Mellitus><Type II diabetes><Vaccines><Viral><Viral Burden><Viral Diseases><Viral Gastroenteritis><Viral Load><Viral Load result><Viral Respiratory Tract Infection><Virus><Virus Diseases><Work><Wuhan coronavirus><adaptive immune response><adaptive immunity><adiposity><adult onset diabetes><adulthood><alimentary tract><antibody biosynthesis><biological signal transduction><bowel><compare to control><comparison control><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19 virus><corpulence><detection limit><diet-associated obesity><diet-induced obesity><diet-related obesity><diets><digestive canal><disease severity><enteric viral infection><enteric virus infection><extreme obesity><feeding><flow cytophotometry><global health><hCoV19><heart disorder><heavy metal Pb><heavy metal lead><host response><immune system function><immune system response><immunoglobulin biosynthesis><immunoresponse><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><innovate><innovation><innovative><insight><intestinal epithelium><ketosis resistant diabetes><kidney disorder><lFN-Gamma><maturity onset diabetes><metabolism disorder><mortality><mouse model><murine model><nCoV2><novel><ob/ob mouse><obese patients><pathogen><pathway><patients with obesity><protective factors><pulmonary><receptor expression><renal disorder><response><secondary lymph organ><secondary lymphatic organ><secondary lymphoid organ><social role><stool><translational opportunities><translational potential><type 2 DM><type II DM><type two diabetes><viral infection><viral respiratory infection><virus infection><virus-induced disease>