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Identification of the major genetic determinant for neurovirulence of tick-borne orbiviruses
P A Nuttall1, S R Moss, L D Jones
1N.E.R.C. Institute of Virology, Oxford, United Kingdom.
Abstract:
Three members of the Great Island antigenic subgroup (Kemerovo serogroup) of tick-borne obiviruses produced fatal infections following intracerebral inculation of 2-day-old mice. The average survival times and PFU/LD50 ratios of mice inoculated with Wexford (WEX) virus were significantly greater than those of either Nugget (NUG) or Great Island (GI) virus. Reassortant viruses were isolated following dual infections of cell cultures with a spontaneous temperature-sensitive (ts) mutant of WEX virus, and either NUG wild-type virus or a ts mutant of GI virus. The neurovirulence for mice and derivation of the genomic RNA segments were determined for the reassortants. Analysis of this data revealed that the pathogenic phenotype of the reassortant viruses depended on the parental origin of genomic segment 4. The major genetic determinant of serotype specificity was not shown to influence neurovirulence in these investigations.
Insights
Tick-borne orbiviruses can cause fatal infections in mice. A specific gene segment (segment 4) was identified as crucial for the neurovirulence of these Wexford (WEX) and related viruses.
Area of Science:
- Virology
- Neuroscience
- Genetics
Background:
- Tick-borne orbiviruses, including those in the Kemerovo serogroup, are significant pathogens.
- Fatal infections can result from intracerebral inoculation of young mice with certain orbiviruses.
- Wexford (WEX) virus exhibits different virulence characteristics compared to Nugget (NUG) and Great Island (GI) viruses.
Purpose of the Study:
- To investigate the genetic basis of neurovirulence in tick-borne orbiviruses.
- To identify specific viral genomic segments responsible for pathogenic phenotypes.
- To understand the relationship between serotype specificity and neurovirulence.
Main Methods:
- Generation of reassortant orbiviruses through dual infections of cell cultures using temperature-sensitive mutants.
- Intracerebral inoculation of 2-day-old mice with parental and reassortant viruses.
- Determination of neurovirulence (survival time, PFU/LD50 ratios) and genomic RNA segment origins for reassortants.
Main Results:
- Reassortant viruses were successfully created from WEX, NUG, and GI viruses.
- Neurovirulence of reassortant viruses was dependent on the parental origin of genomic segment 4.
- Wexford (WEX) virus demonstrated significantly longer survival times and higher PFU/LD50 ratios compared to NUG and GI viruses.
Conclusions:
- Genomic segment 4 is a critical determinant of neurovirulence in this group of tick-borne orbiviruses.
- Serotype specificity, determined by other genetic factors, did not directly correlate with neurovirulence in this study.
- These findings contribute to understanding orbivirus pathogenesis and genetic determinants of disease.