title: Impaired wound healing predisposes obese mice to severe influenza virus infection.
abstract: For the first time, obesity appeared as a risk factor for developing severe 2009 pandemic influenza infection. Given the increase in obesity, there is a need to understand the mechanisms underlying poor outcomes in this population. In these studies, we examined the severity of pandemic influenza virus in obese mice and evaluated antiviral effectiveness. We found that genetically and diet-induced obese mice challenged with either 2009 influenza A virus subtype H1N1 or 1968 subtype H3N2 strains were more likely to have increased mortality and lung pathology associated with impaired wound repair and subsequent pulmonary edema. Antiviral treatment with oseltamivir enhanced survival of obese mice. Overall, these studies demonstrate that impaired wound lung repair in the lungs of obese animals may result in severe influenza virus infection. Alternative approaches to prevention and control of influenza may be needed in the setting of obesity.
authors.affiliation: Microbiology Doctoral Training Program, University of Wisconsin, Madison, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: O'Brien
authors.forename: Peter
authors.initials: P
authors.lastname: Vogel
authors.forename: Susu
authors.initials: S
authors.lastname: Duan
authors.forename: Elena A
authors.initials: EA
authors.lastname: Govorkova
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Webby
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: McCullers
authors.forename: Stacey
authors.initials: S
authors.lastname: Schultz-Cherry
mesh_terms: D000418:Albumins / Q000032:analysis; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D053118:Influenza A Virus, H1N1 Subtype; D053122:Influenza A Virus, H3N2 Subtype; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000378:metabolism; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000473:pathology* / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009000:Monocytes; D020556:Neutrophil Infiltration; D009765:Obesity / Q000150:complications* / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D053139:Oseltamivir / Q000627:therapeutic use*; D011654:Pulmonary Edema / Q000821:virology; D012720:Severity of Illness Index; D019562:Viral Load; D014945:Wound Healing
chemical_list: D000418:Albumins; D000998:Antiviral Agents; D019394:Ki-67 Antigen; D053139:Oseltamivir