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In Vitro Analysis of Myd88-mediated Cellular Immune Response to West Nile Virus Mutant Strain Infection
Published on: November 27, 2014
Tissue tropism and neuroinvasion of West Nile virus do not differ for two mouse strains with different survival rates
Ashley N Brown1, Kim A Kent, Corey J Bennett
1Wadsworth Center, New York State Department of Health, P.O. Box 509, Albany, NY 12201-0509, USA.
Abstract:
West Nile virus (WNV) is a mosquito-borne flavivirus that infects the central nervous system of humans and other animals. In this study, we found that C3H/HeN (C3H) mice exhibited a higher morbidity and mortality than C57BL/6 (B6) mice. We compared tissue tropism, viral replication and kinetics for C3H and B6 mice during acute viral infection. WNV was detected in multiple tissues, including novel sites such as the skin, duodenum and pancreas, but the tropism was identical for the two strains. Additionally, viral load and kinetics of spread did not differ substantially between strains. Neuroinvasion occurred in both strains by day 3 post-inoculation with early detection in the olfactory bulbs and spinal cord, suggesting that WNV neuroinvades at specific sites. Furthermore, neuroinvasion and viral load in the CNS did not predict disease outcome. Our data suggest that the disparities in morbidity and mortality between C3H and B6 mice are not due to differences in tropism, viral load or kinetics during acute WNV infection.
Insights
Differences in West Nile virus (WNV) disease severity between mouse strains are not explained by viral spread or central nervous system (CNS) invasion. Tropism, viral load, and kinetics did not differ between C3H and B6 mice.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- West Nile virus (WNV) is a significant mosquito-borne flavivirus impacting public health.
- WNV infection targets the central nervous system (CNS) in humans and animals.
- Mouse models are crucial for understanding WNV pathogenesis.
Purpose of the Study:
- To investigate the factors contributing to differential WNV disease outcomes in C3H/HeN (C3H) versus C57BL/6 (B6) mice.
- To compare tissue tropism, viral replication, and kinetics of WNV infection between C3H and B6 mouse strains.
- To determine if neuroinvasion or viral load in the CNS correlates with disease severity.
Main Methods:
- Comparative analysis of WNV infection in C3H and B6 mice.
- Detection and quantification of WNV in various tissues.
- Assessment of viral kinetics and neuroinvasion.
- Correlation of viral parameters with morbidity and mortality.
Main Results:
- WNV was detected in novel tissues including skin, duodenum, and pancreas, with identical tropism in both mouse strains.
- Viral load and kinetics of spread were not substantially different between C3H and B6 mice.
- Neuroinvasion occurred in both strains by day 3, with early detection in olfactory bulbs and spinal cord, but did not predict disease outcome.
Conclusions:
- Disparities in WNV-induced morbidity and mortality between C3H and B6 mice are not attributable to differences in viral tropism, load, or kinetics.
- Specific sites of neuroinvasion were identified, but did not correlate with disease severity.
- Further research is needed to elucidate the mechanisms underlying differential WNV pathogenesis between mouse strains.
