Acute Phase Extrapulmonary Effects of a High-Dose Influenza A Virus Infection in a Mouse Model of Obesity

Influenza A viruses (IAVs) primarily cause respiratory illness but can also induce extrapulmonary effects, which may be aggravated by obesity. This study evaluated the impact of obesity on virus replication, histopathological changes, and cytokine/chemokine profiles in extrapulmonary sites during the acute phase, following a high-dose IAV infection. Diet-induced non-obese mice or mice with obesity were inoculated intranasally with either vehicle (medium) or 10³ TCID₅₀ of the 2009 pandemic H1N1 IAV. At 3 days post-infection (dpi), the lungs, blood, and various extrapulmonary tissues were collected for virus titration, histopathological analysis, and cytokine/chemokine quantification. IAV infection resulted in comparable virus titers (6-7 log₁₀ TCID₅₀/mL) and histopathological scores (p > 0.05 in each case) in the lungs of mice with or without obesity. Replicating viruses were not detected in the extrapulmonary sites, and histopathological scores did not differ significantly between the two groups. However, analysis of fold changes in five cytokines/chemokines (i.e., IL-6, IL-1β, TNFα, MCP-1, and IFNγ) revealed site-specific differences. IL-6 was significantly higher (p < 0.05) in the lungs and perirenal adipose tissue, and showed a higher trend in the kidney (0.05 ≤ p ≤ 0.1); IL-1β had a higher trend in the lungs; TNFα was significantly lower in the kidney but showed a higher trend in the lungs; while MCP-1 was significantly lower in the lungs, plasma, and inguinal adipose tissue of mice with obesity compared to non-obese mice. Future studies should consider a broader range of IAV strains/subtypes, doses, time points, and inflammatory markers to better understand how obesity affects extrapulmonary outcomes.