Abstract: TH-PO262

Implications of Short-Term Coxsackievirus Infection in Non-Obese Diabetic Mouse Kidneys

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Walter, Debra L., Ohio University, Athens, Ohio, United States
  • Oaks, Rosemary J, Ohio University, Athens, Ohio, United States
  • Malgor, Ramiro, Ohio University, Athens, Ohio, United States
  • Schwartz, Frank L., Ohio University, Athens, Ohio, United States
  • Mccall, Kelly D., Ohio University, Athens, Ohio, United States
  • Coschigano, Karen T., Ohio University, Athens, Ohio, United States
Background

End stage renal disease (ESRD) can result from four primary diagnoses, diabetes, hypertension, glomerulonephritis and cystic kidney disease, all of which have viruses implicated as causative agents. Enteroviruses, like coxsackievirus (CV), are a common genus of viruses that have been implicated in both diabetes and cystic kidney disease, however, little is known about early CV infection in the kidney and how that infection may contribute to ESRD. This study, therefore, evaluates short-term CV infection in the kidneys of non-obese diabetic (NOD) mice; a strain of mice with a genetic predisposition to develop type 1 diabetes mellitus (the most common primary ESRD diagnosis), a condition which can be accelerated by CV infection in these mice. Characterizing the short-term effects of CV on the kidneys will define our understanding of how “innocent” viruses like CV may have a more significant impact on chronic kidney disease than previously described.

Methods

Eight-week-old NOD mice were infected with CV and euthanized 3, 7, 10 and 14 days post infection. Kidneys were collected and processed for histological and gene expression analyses.

Results

CV RNA in the kidney peaked 3 days post infection and was identified in both the glomerulus and tubulointerstitial regions. Virus was no longer detectible by real-time RT-PCR or in situ hybridization 14 days post infection. Percent kidney weight and urinary albumin creatinine ratio, hallmarks of kidney injury, did not demonstrate significant alterations in NOD mouse kidneys at these timepoints. Histological evaluation of PAS and H&E stained tissue did not reveal any significant pathological changes between infected and non-infected kidneys at any time point. However, gene expression of TLR3 and its signaling products TNFα, IL-6 and CXCL10 were found to be upregulated 3 days post CV infection, indicating a potential kidney cell response to virus infection. Further evaluation will be performed to determine in which cells of the kidney TLR3 is upregulated.

Conclusion

Together, these data will help identify initial kidney gene expression changes in response to virus infection that may play a role in later ESRD.