In 2022 partners from TBFVnet published two important research papers. The first was released in April and was the result of the work of the Molecular Virology Laboratory at ICGEB. The second was published in November as a joint effort between the Biomedical Research Center, the Slovak Academy of Sciences and the lead partner, the Veterinary Research Institute in the Czech Republic. Each paper investigates two different aspects of research on tick-borne flaviviruses.
The first study focuses on the possibility to develop a new antiviral against flaviviruses. Antivirals are a specific class of drugs useful to treat viral diseases. They can only be used within the very first hours at the onset of the infection as later they start losing their effectiveness. Compared to the number of viruses that can infect humans, very few of these drugs are available, among which those against prominent endemic viruses such as influenza, HIV, hepatitis C and herpesviruses.
Antiviral drugs do not kill the virus as some antibiotics do with bacteria. Usually, they act by impairing virus replication within the cell or its ability to infect other cells. This is why they need to be given to the patient at the onset of infection: the sooner they act, the earlier they can block the spread of the virus in the body. But this is also the reason why antivirals are few and difficult to develop. To replicate and proliferate viruses use the host cellular machinery, the same mechanisms that are present in healthy cells. Thus, if antivirals are not carefully developed, they can be toxic and harmful to the human body. But there is another possibility, at least against one class of viruses.
Most viruses have a closed protein structure containing their genetic material, but some share a peculiar lipidic envelope surrounding the core. It is through this membrane that these viruses enter the cell and infect them. This is a characteristic of all flaviviruses, including those carried by ticks. A drug targeting this envelope, or any of the steps in which it is involved, could represent a precious tool. It could serve as a broad treatment for a whole class of viruses while we wait for vaccines or more specific antivirals to be developed. However, in the most promising scenario, they can also be used as a first-line defence against emerging infections.
ICGEB researchers explored the role of recently synthetic chemical compounds, derived from a molecule called pyridobenzothiazolone, in reducing viral infection by West Nile virus, a flavivirus that represents a serious threat to human health. The study, published in the journal Viruses, confirmed the role of this compound in inhibiting infection from the virus. Although the mechanism of action is not fully elucidated, this research confirms that these chemical compounds can act on the virus envelope. This opens the way to the development of antiviral drugs against all flaviviruses including those carried by ticks such as tick-borne encephalitis virus.
The second research project presented a new tool to investigate the interaction between a virus and its vector deeply. In particular, the authors from the TBFVnet partner institutions, the Biomedical Research Center and the Veterinary Research Institute, experimented with a new procedure to study the interaction between tick-borne encephalitis virus (TBEV) and the tick. In fact, very little is known about how these two organisms live and share their life cycle. TBEV can live within the ticks without harming the tick in any way and from there infect humans and animals. This partnership is, indeed, at the basis of the cycle that transmits the virus to all its hosts including humans. Understanding how the virus lives and replicates in ticks and is then transmitted to the hosts could be pivotal in finding new therapies or strategies to prevent infection.
The researchers used an engineered version of TBEV that carries the mCherry reporter gene and tests its efficacy to study different stages of tick and virus interaction. A reporter gene can in fact shed light on specific molecular mechanisms; it can be seen through microscopy as it emits light when stimulated and researchers can thus monitor the virus’ presence in any experiment. This study confirmed that the TBEV mCherry is a valuable tool for studying the biological mechanisms between the virus and the tick. With this new tool, it could be possible to better understand the biology of TBEV and, in future, find new ways to block its infection.
These two studies represent precious milestones for the TBFVnet project. The research that can be done in this field can effectively give new solutions to the threat that flaviviruses carried by ticks represent to human health.
The research papers cited in the article can be found at the following links:
- Virucidal Activity of the Pyridobenzothiazolone Derivative HeE1-17Y against Enveloped RNA Viruses. Bonotto et al., Viruses 2022 doi: 10.3390/v14061157
- Fitness of mCherry Reporter Tick-Borne Encephalitis Virus in Tick Experimental Models. Kevély et al., Viruses 2022, doi: 10.3390/v14122673
