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The Use of Ex Vivo Organ Cultures in Tick-Borne Virus Research
Jeffrey M Grabowski1, Danielle K Offerdahl1, Marshall E Bloom1
1Biology of Vector-Borne Viruses Section, Laboratory of Virology , Rocky Mountain Laboratories, NIAID/NIH , 903 South Fourth Street , Hamilton , Montana 59840 , United States.
Abstract:
Each year there are more than 15 000 cases of human disease caused by infections with tick-borne viruses (TBVs). These illnesses occur worldwide and can range from very mild illness to severe encephalitis and hemorrhagic fever. Although TBVs are currently identified as neglected vector-borne pathogens and receive less attention than mosquito-borne viruses, TBVs are expanding into new regions, and infection rates are increasing. Furthermore, effective vaccines, diagnostic tools, and other countermeasures are limited. The application of contemporary technologies to TBV infections presents an excellent opportunity to develop improved, effective countermeasures. Experimental tick and mammal models of infection can be used to characterize determinants of infection, transmission, and virulence and to test candidate countermeasures. The use of ex vivo tick cultures in TBV research provides a unique way to look at infection in specific tick organs. Mammal ex vivo organ slice and, more recently, organoid cultures are additional models that can be used to elucidate direct tissue-specific responses to infection. These ex vivo model systems are convenient for testing methods involving transcript knockdown and small molecules under tightly controlled conditions. They can also be combined with in vitro and in vivo studies to tease out possible host factors and potential vaccine or therapeutic candidates. In this brief perspective, we describe how ex vivo cultures can be combined with modern technologies to advance research on TBV infections.
Insights
Tick-borne virus (TBV) infections are a growing global health concern with limited countermeasures. This research explores how advanced ex vivo models can accelerate the development of new vaccines and treatments for these neglected pathogens.
Area of Science:
- Virology
- Infectious Diseases
- Public Health
Background:
- Tick-borne viruses (TBVs) cause over 15,000 human diseases annually worldwide, ranging from mild illness to severe encephalitis and hemorrhagic fever.
- TBVs are increasingly recognized as neglected pathogens, receiving less attention than mosquito-borne viruses, despite expanding geographic ranges and rising infection rates.
- Current effective vaccines, diagnostic tools, and countermeasures for TBV infections remain limited.
Purpose of the Study:
- To highlight the potential of contemporary technologies, particularly ex vivo model systems, for advancing research on tick-borne virus infections.
- To explore how these advanced models can facilitate the development of improved and effective countermeasures against TBVs.
- To emphasize the need for increased focus on TBVs as a significant public health threat.
Main Methods:
- Utilizing experimental tick and mammal models to characterize infection determinants, transmission, and virulence.
- Employing ex vivo tick organ cultures to examine TBV infection within specific tick tissues.
- Leveraging ex vivo mammal organ slice and organoid cultures to study direct, tissue-specific responses to infection.
- Integrating ex vivo systems with in vitro and in vivo studies for comprehensive analysis.
Main Results:
- Ex vivo model systems offer a controlled environment for testing interventions like transcript knockdown and small molecules.
- These models facilitate the elucidation of direct tissue-specific responses to TBV infections.
- The combination of ex vivo, in vitro, and in vivo approaches aids in identifying host factors and potential vaccine or therapeutic candidates.
Conclusions:
- Ex vivo cultures, when combined with modern technologies, represent a powerful approach to accelerate TBV research.
- These advanced models can significantly contribute to the development of novel countermeasures, including vaccines and therapeutics.
- Further research utilizing these integrated systems is crucial for addressing the growing threat of tick-borne viral diseases.
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