The most insidious pandemic of modern life does not arise from an infectious agent but rather from malnutrition. With its global incidence tripling over the past three decades, obesity is a major public health concern. Obesity’s rising prevalence has also illuminated its impact on communicable diseases. Following the 2009 H1N1 influenza A virus pandemic, obesity was identified as a risk factor for increased disease severity and mortality in infected individuals. Obesity causes a chronic state of meta-inflammation with systemic implications for immunity, including delayed antiviral responses to influenza virus infection, poor recovery, and impaired immunological memory. However, the majority of past work neglected the innate responses, especially the impact on the epithelium. To better understand the innate response to influenza infection, obese animal models and human respiratory epithelial cells were inoculated with influenza viruses to quantify the innate responses. In obese hosts, antiviral effector production, including type I and type III interferons, was consistently blunted across all model systems and linked to a highly oxidative, pro-inflammatory environment. This interferon-deficient state altered the host microenvironment in which influenza replicated, spread, and caused disease. Due to the inherent mutability and segmented nature of influenza virus, this altered microenvironment also had implications for the genetic drift and shift of the viral population. Compared to infection of lean hosts, minor variants rapidly emerged within the viral population in obese hosts which exhibited increased viral replication, enhanced virulence, and antiviral resistance. The delayed action of interferon also permitted greater rates of reassortment. Together, this suggested obesity permitted the emergence of novel, and potentially pathogenic, viral variants. Influenza viruses pose constant seasonal and pandemic threats with high morbidity and mortality suffered by overweight and obese patients. If current trends continue, nearly half of the worldwide population will be obese by 2050. This population will have growing impacts on both non-communicable and communicable diseases and may affect global evolutionary trends of influenza virus.
","abstract_html":"<p>The most insidious pandemic of modern life does not arise from an infectious agent but rather from malnutrition. With its global incidence tripling over the past three decades, obesity is a major public health concern. Obesity’s rising prevalence has also illuminated its impact on communicable diseases. Following the 2009 H1N1 influenza A virus pandemic, obesity was identified as a risk factor for increased disease severity and mortality in infected individuals. Obesity causes a chronic state of meta-inflammation with systemic implications for immunity, including delayed antiviral responses to influenza virus infection, poor recovery, and impaired immunological memory. However, the majority of past work neglected the innate responses, especially the impact on the epithelium. To better understand the innate response to influenza infection, obese animal models and human respiratory epithelial cells were inoculated with influenza viruses to quantify the innate responses. In obese hosts, antiviral effector production, including type I and type III interferons, was consistently blunted across all model systems and linked to a highly oxidative, pro-inflammatory environment. This interferon-deficient state altered the host microenvironment in which influenza replicated, spread, and caused disease. Due to the inherent mutability and segmented nature of influenza virus, this altered microenvironment also had implications for the genetic drift and shift of the viral population. Compared to infection of lean hosts, minor variants rapidly emerged within the viral population in obese hosts which exhibited increased viral replication, enhanced virulence, and antiviral resistance. The delayed action of interferon also permitted greater rates of reassortment. Together, this suggested obesity permitted the emergence of novel, and potentially pathogenic, viral variants. Influenza viruses pose constant seasonal and pandemic threats with high morbidity and mortality suffered by overweight and obese patients. If current trends continue, nearly half of the worldwide population will be obese by 2050. This population will have growing impacts on both non-communicable and communicable diseases and may affect global evolutionary trends of influenza virus.</p>","abstract_has_math":false,"creators":["Honce, Rebekah Reed"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biomedical Sciences","degree_department":null,"school":null,"contributors":["Stacey Schultz-Cherry, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-11-01T07:00:00Z","date_published":"2020-11-01T07:00:00Z","updated_at":"2026-07-24T05:00:45Z","subjects":["Evolution","Influenza","Interferon","Obesity","Quasispecies","Reassortment","Biochemical Phenomena, Metabolism, and Nutrition","Diseases","Medical Cell Biology","Medical Sciences","Medicine and Health Sciences","Public Health","Virus Diseases"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dc.uthsc.edu/dissertations/538","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Stacey Schultz-Cherry, PhD"]},{"key":"dc:creator","label":"Author","values":["Honce, Rebekah Reed"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2022-11-12T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Sciences"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Evolution","Influenza","Interferon","Obesity","Quasispecies","Reassortment","Biochemical Phenomena, Metabolism, and Nutrition","Diseases","Medical Cell Biology","Medical Sciences","Medicine and Health Sciences","Public Health","Virus Diseases"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dc.uthsc.edu/dissertations/538"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The most insidious pandemic of modern life does not arise from an infectious agent but rather from malnutrition. With its global incidence tripling over the past three decades, obesity is a major public health concern. Obesity’s rising prevalence has also illuminated its impact on communicable diseases. Following the 2009 H1N1 influenza A virus pandemic, obesity was identified as a risk factor for increased disease severity and mortality in infected individuals. Obesity causes a chronic state of meta-inflammation with systemic implications for immunity, including delayed antiviral responses to influenza virus infection, poor recovery, and impaired immunological memory. However, the majority of past work neglected the innate responses, especially the impact on the epithelium. To better understand the innate response to influenza infection, obese animal models and human respiratory epithelial cells were inoculated with influenza viruses to quantify the innate responses. In obese hosts, antiviral effector production, including type I and type III interferons, was consistently blunted across all model systems and linked to a highly oxidative, pro-inflammatory environment. This interferon-deficient state altered the host microenvironment in which influenza replicated, spread, and caused disease. Due to the inherent mutability and segmented nature of influenza virus, this altered microenvironment also had implications for the genetic drift and shift of the viral population. Compared to infection of lean hosts, minor variants rapidly emerged within the viral population in obese hosts which exhibited increased viral replication, enhanced virulence, and antiviral resistance. The delayed action of interferon also permitted greater rates of reassortment. Together, this suggested obesity permitted the emergence of novel, and potentially pathogenic, viral variants. Influenza viruses pose constant seasonal and pandemic threats with high morbidity and mortality suffered by overweight and obese patients. If current trends continue, nearly half of the worldwide population will be obese by 2050. This population will have growing impacts on both non-communicable and communicable diseases and may affect global evolutionary trends of influenza virus.
"]},{"key":"dc:title","label":"Title","values":["Attenuation of Interferon Responses in the Obese Host and Ramifications for Influenza Virus Evolution"]}]}],"canonical_facts":{"dc:contributor":["Stacey Schultz-Cherry, PhD"],"dc:creator":["Honce, Rebekah Reed"],"dc:date.available":["2022-11-12T08:00:00Z"],"dc:description.abstract":["The most insidious pandemic of modern life does not arise from an infectious agent but rather from malnutrition. With its global incidence tripling over the past three decades, obesity is a major public health concern. Obesity’s rising prevalence has also illuminated its impact on communicable diseases. Following the 2009 H1N1 influenza A virus pandemic, obesity was identified as a risk factor for increased disease severity and mortality in infected individuals. Obesity causes a chronic state of meta-inflammation with systemic implications for immunity, including delayed antiviral responses to influenza virus infection, poor recovery, and impaired immunological memory. However, the majority of past work neglected the innate responses, especially the impact on the epithelium. To better understand the innate response to influenza infection, obese animal models and human respiratory epithelial cells were inoculated with influenza viruses to quantify the innate responses. In obese hosts, antiviral effector production, including type I and type III interferons, was consistently blunted across all model systems and linked to a highly oxidative, pro-inflammatory environment. This interferon-deficient state altered the host microenvironment in which influenza replicated, spread, and caused disease. Due to the inherent mutability and segmented nature of influenza virus, this altered microenvironment also had implications for the genetic drift and shift of the viral population. Compared to infection of lean hosts, minor variants rapidly emerged within the viral population in obese hosts which exhibited increased viral replication, enhanced virulence, and antiviral resistance. The delayed action of interferon also permitted greater rates of reassortment. Together, this suggested obesity permitted the emergence of novel, and potentially pathogenic, viral variants. Influenza viruses pose constant seasonal and pandemic threats with high morbidity and mortality suffered by overweight and obese patients. If current trends continue, nearly half of the worldwide population will be obese by 2050. This population will have growing impacts on both non-communicable and communicable diseases and may affect global evolutionary trends of influenza virus.
"],"dc:identifier":["https://dc.uthsc.edu/dissertations/538"],"dc:subject":["Evolution","Influenza","Interferon","Obesity","Quasispecies","Reassortment","Biochemical Phenomena, Metabolism, and Nutrition","Diseases","Medical Cell Biology","Medical Sciences","Medicine and Health Sciences","Public Health","Virus Diseases"],"dc:title":["Attenuation of Interferon Responses in the Obese Host and Ramifications for Influenza Virus Evolution"],"thesis:degree_discipline":["Biomedical Sciences"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:00:45Z"}