Abstract
BackgroundWest Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans. Herein, we investigated the immunological responses induced by two phylogenetically related WNV strains of lineage 1, WNV NY99, and WNV Eg101.MethodsEight-week-old C57BL/6J mice were inoculated with WNV NY99 or WNV Eg101 and mortality, virus burden in the periphery and brain, type 1 interferon response, WNV-specific antibodies, leukocyte infiltration, and inflammatory responses were analyzed.ResultsAs expected, WNV NY99 infected mice demonstrated high morbidity and mortality, whereas no morbidity and mortality was observed in WNV Eg101 infected mice. Virus titers were comparable in the serum of both WNV NY99 and WNV Eg101 infected mice at day 3 after inoculation; however, at day 6, the virus was cleared from WNV Eg101 infected mice but the virus titer remained high in the WNV NY99 infected mice. Virus was detected in the brains of both WNV NY99 and Eg101 infected mice, albeit significantly higher in the brains of WNV NY99 infected mice. Surprisingly, levels of type 1 interferon and WNV-specific antibodies were significantly higher in the serum and brains of WNV NY99 infected mice. Similarly, protein levels of multiple cytokines and chemokines were significantly higher in the serum and brains of WNV NY99 infected mice. In contrast, we observed significantly higher numbers of innate and adaptive immune cells in the spleens and brains of WNV Eg101 infected mice. Moreover, total number and percentage of IFN-γ and TNF-α producing WNV-specific CD8+ T cells were also significantly high in WNV Eg101 infected mice.ConclusionsOur data demonstrate that induction of virus-specific effector immune cell response limits virus replication and severe WNV disease in Eg101 infected mice. Our data also demonstrate an inverse correlation between leukocyte accumulation and production of pro-inflammatory mediators in WNV-infected mice. Moreover, increased production of pro-inflammatory mediators was associated with high-virus titers and increased mortality in WNV NY99 infected mice.
Highlights
West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans
We have previously demonstrated that mice immunized with both 1000 and 100 plaque-forming units (PFU) of WNV Eg101 demonstrated 100 % protection against both subcutaneous and intracranial challenge with a lethal dose (1000 PFU) of the WNV NY99 strain [17]
We examined the immunological changes in the serum and brain of mice during WNV NY99 strain and WNV Eg101 strain infection to understand the underlying immunopathological mechanisms leading to severe WNV disease
Summary
West Nile virus (WNV) is a neurotropic flavivirus that has emerged globally as a significant cause of viral encephalitis in humans. West Nile virus (WNV), a neurotropic flavivirus, has emerged as a significant cause of viral encephalitis in the USA [1]. WNV infection in humans is usually asymptomatic or self-limiting, with a mild febrile illness, but may progress to meningitis, encephalitis, paralysis, and death. Until 1999, WNV was geographically distributed in Africa, the Middle East, western and central Asia, India, and Europe, where it caused sporadic cases of febrile disease and occasional outbreaks of encephalitis in elderly people and in equines [2, 3]. Recent outbreaks of highly virulent WNV strains have been reported in the Mediterranean basin, southern Europe, and Russia [6, 7]. The worldwide incidence of WNV infection is increasing, there is no specific treatment or vaccine available for use in humans
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
