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Published on: November 1, 2011
Reverted virulence of attenuated tick-borne encephalitis virus mutant is not accompanied with the changes in deduced
M Kaluzová1, E Elecková, E Zuffová
1Institute of Virology, Slovak Academy of Sciences, Bratislava.
Abstract:
Serial passages of tick-borne encephalitis (TBE) virus strain 4387 isolated from the liver and lungs of the bank vole through the salivary glands of Ixodes ricinus ticks led to a reduction of its virulence for laboratory mice infected via peripheral route. When attenuated mutants were passaged through mouse brains, virulent phenotypes have appeared in the 3rd mouse passage. After 5 consecutive passages the virus was more pathogenic for mice after peripheral inoculation than the parental 4387 strain. The nucleotide sequence of the envelope proteins of the strain 4387 was studied after passaging through ticks salivary glands and subsequently through mice. The sequences coding for the envelope protein E of the virus from the first, third and fifth mouse passages were compared with those of parental virus and mutant attenuated in ticks. The attenuated mutant differing from the parental strain 4387 by the amino acid substitution from glutamic acid to lysine at position 84, and from isoleucine to threonine at amino acid position 319 revealed strongly reduced pathogenicity for adult laboratory mice after peripheral inoculation. The attenuated mutant regained its virulence after 3 - 5 mouse brain passages, but the two amino acid substitutions were still conserved.
Insights
Attenuating tick-borne encephalitis virus (TBEV) in ticks reduced its virulence in mice. However, passaging the virus through mouse brains restored its pathogenicity, revealing conserved genetic changes.
Area of Science:
- Virology
- Pathogen Evolution
- Neuroscience
Background:
- Tick-borne encephalitis virus (TBEV) is a significant human pathogen transmitted by Ixodes ticks.
- Understanding TBEV virulence and attenuation mechanisms is crucial for developing effective countermeasures.
Purpose of the Study:
- To investigate the genetic basis of TBEV virulence changes after passaging through tick salivary glands and mouse brains.
- To compare the envelope protein E sequences of attenuated and virulent TBEV strains.
Main Methods:
- Serial passaging of TBEV strain 4387 in Ixodes ricinus ticks and subsequent inoculation in laboratory mice.
- Nucleotide sequencing of the TBEV envelope protein E gene after different passages.
- Assessment of viral pathogenicity in mice via peripheral inoculation.
Main Results:
- Passaging TBEV in tick salivary glands attenuated the virus in mice.
- Subsequent passaging in mouse brains led to the reappearance of virulent phenotypes.
- An attenuated mutant with specific amino acid substitutions (E84K, I319T) showed reduced pathogenicity, which was conserved even after virulence restoration.
Conclusions:
- TBEV can regain virulence after mouse brain passages, despite retaining specific amino acid substitutions.
- These findings highlight the complex interplay between host environments and viral evolution in determining TBEV pathogenicity.
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