Impaired virus clearance, compromised immune response and increased mortality in type 2 diabetic mice infected with West Nile virus

PLoS One. 2012;7(8):e44682. doi: 10.1371/journal.pone.0044682. Epub 2012 Aug 31.


Clinicoepidemiological data suggest that type 2 diabetes is associated with increased risk of West Nile virus encephalitis (WNVE). However, no experimental studies have elucidated the role of diabetes in WNV neuropathogenesis. Herein, we employed the db/db mouse model to understand WNV immunopathogenesis in diabetics. Nine-week old C57BL/6 WT and db/db mice were inoculated with WNV and mortality, virus burden in the periphery and brain, and antiviral defense responses were analyzed. db/db mice were highly susceptible to WNV disease, exhibited increased tissue tropism and mortality than the wild-type mice, and were unable to clear the infection. Increased and sustained WNV replication was observed in the serum, peripheral tissues and brain of db/db mice, and heightened virus replication in the periphery was correlated with enhanced neuroinvasion and replication of WNV in the brain. WNV infection in db/db mice was associated with enhanced inflammatory response and compromised antiviral immune response characterized by delayed induction of IFN-α, and significantly reduced concentrations of WNV-specific IgM and IgG antibodies. The compromised immune response in db/db mice correlated with increased viremia. These data suggest that delayed immune response coupled with failure to clear the virus leads to increased mortality in db/db mice. In conclusion, this study provides unique mechanistic insight into the immunopathogenesis of WNVE observed in diabetics and can be used to develop therapeutics for the management of WNVE among diabetic patients.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue / pathology
  • Adipose Tissue / virology
  • Animals
  • Antibodies, Viral / immunology
  • Antibody Formation / immunology
  • Body Weight
  • Brain / pathology
  • Brain / virology
  • Chemokines / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / immunology*
  • Diabetes Mellitus, Type 2 / virology*
  • Disease Susceptibility / complications
  • Disease Susceptibility / immunology
  • Disease Susceptibility / pathology
  • Disease Susceptibility / virology
  • Glucose Intolerance / blood
  • Glucose Intolerance / complications
  • Glucose Intolerance / immunology
  • Glucose Intolerance / virology
  • Glucose Tolerance Test
  • Immunity / immunology*
  • Interferon-alpha / blood
  • Kinetics
  • Mice
  • Mice, Inbred C57BL
  • Species Specificity
  • Survival Analysis
  • Viral Load
  • Virus Replication
  • West Nile Fever / blood
  • West Nile Fever / complications
  • West Nile Fever / immunology*
  • West Nile Fever / virology*
  • West Nile virus / immunology*
  • West Nile virus / physiology


  • Antibodies, Viral
  • Chemokines
  • Interferon-alpha