MicroRNA-based control of tick-borne flavivirus neuropathogenesis: Challenges and perspectives

Antiviral Research
Natalya L TeterinaAlexander G Pletnev

Abstract

In recent years, microRNA-targeting has become an effective strategy for selective control of tissue-tropism and pathogenicity of both DNA and RNA viruses. Previously, we reported the successful application of this strategy to control the neurovirulent phenotype of a model chimeric tick-borne encephalitis/dengue type 4 virus (TBEV/DEN4), containing the structural protein genes of a highly virulent TBEV in the genetic backbone of non-neuroinvasive DEN4 virus. In the present study, we investigated the suitability of this approach for the attenuation of the more neurovirulent chimeric virus (TBEV/LGTV), which is based on the genetic backbone of the naturally attenuated member of the TBEV serocomplex, a Langat virus (LGTV). Unlike the TBEV/DEN4, the TBEV/LGTV virus retained the ability of its parental viruses to spread from the peripheral site of inoculation to the CNS. We evaluated ten potential sites in the 3'NCR of the TBEV/LGTV genome for placement of microRNA (miRNA) targets and found that the TBEV/LGTV genome is more restrictive for such genetic manipulations compared to TBEV/DEN4. In addition, unlike TBEV/DEN4 virus, the introduction of multiple miRNA targets into either the 3'NCR or ORF of the TBEV/LGTV genome had only a mo...Continue Reading

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Citations

Dec 14, 2018·Clinical Microbiology Reviews·Gábor Kemenesi, Krisztián Bányai
May 8, 2018·Viruses·Yongxiu YaoVenugopal Nair
Apr 13, 2021·Frontiers in Immunology·Liming JiangQiangming Sun
May 11, 2021·Frontiers in Immunology·Waqas AhmedHameeda Sultana

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