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Science uncovers key features of tick-borne hemorrhagic fever

A recent study discovered the molecular mechanisms of infection of an emerging virus that causes severe hemorrhagic fever.

Tick-borne diseases have been on the rise over the last few decades and are a threat to human health. Lyme disease is the most common and perhaps most well-known tick-borne illness in the United States, but at least 16 other diseases carried by these parasites have been described.

Asian longhorned tick can spread SFTSV

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a virus that has been discovered recently, which can cause severe hemorrhagic fever. The Asian longhorned tick, a livestock pest in East and Central Asia, can spread this virus to humans. Infections seem to prevail among farmers and forest workers, with most patients being 50 years of age or older.

A feature that SFTSV shares with other viruses in the same family is the capability to disable a response from our immune system during an infection. SFTSV infection can cause symptoms that include diarrhea, nausea and muscle pain. The virus has also the ability to prevent blood clotting by depleting platelets while multiplying, leading to hemorrhage.

The outcome of this illness is fatal in approximately 30% of hospitalized patients. This disease first appeared in seven Chinese provinces in 2009. To date, the virus has spread to another seven provinces in China, South Korea, and Japan. While there is no record for SFTSV in the United States yet, nine states have records for the ticks that can carry it.

No therapy currently available for tick-borne hemorrhagic fever

No vaccines or antiviral therapies are currently available to treat the disease because our knowledge of the mechanisms underlying infection is lacking. However, a lack of knowledge of the virus and the emergence of this disease prompted research investigations. A recent study sheds light on SFTSV infection mechanisms and might lead to the development of medications and vaccines in the future. The results of this study are published in Nature Microbiology.

The scientists knew from previous work that SFTSV could evade our immune system thanks to the production of non-structural proteins (NSs). How these proteins work to disable our response to the infection was unclear. In this study, experiments in human cells as well as in mice models demonstrated that viral NSs proteins target another protein within our cells, TPL2. This interaction leads to a series of cellular reactions that cause our body to produce high amounts of a molecule called interleukin 10 (IL10).

IL10 is an anti-inflammatory molecule that limits reactions of the immune systems to prevent self-damage. By making our body produce more IL10, SFTSV causes our immune system to lower its guard and creates the conditions to replicate and cause illness. The researchers then infected mice with SFTSV that was manipulated in a way to block the function of NSs proteins.

These animals developed a milder form of the disease and the majority of them survived. Another approach to stop the infection was to treat infected mice with a substance that would prevent the protein TPL2 from functioning. This experiment also proved successful as most mice recovered from the illness.

Viral and host proteins as candidates for future therapies and vaccines

In conclusion, this study uncovered the mechanisms of infection of SFTSV, which is an emerging virus that causes severe hemorrhagic fever disease and that can spread through tick bites. The virus produces proteins that ultimately reduce the functioning of the immune system and allow infection.

The experiments demonstrated that intervention targeted at the viral proteins NSs and TPL2 protein of the host improved the survival rate of infected mice. These results identify these proteins as targets for the development of drugs and vaccines in humans against a disease that currently has no cure.

Written by Raffaele Camasta, PhD

References

  1. Choi, Y., Park, S.-J., Sun, Y., Yoo, J.-S., Pudupakam, R. S., Foo, S.-S., Shin, W.-J., Chen, S. B., Tsichlis, P. N., Lee, W.-J., Lee, J.-S., Li, W., Brennan, B., Choi, Y.-K., & Jung, J. U. (2019). Severe fever with thrombocytopenia syndrome phlebovirus non-structural protein activates TPL2 signalling pathway for viral immunopathogenesis. Nature Microbiology.
  2. USC science races against tick-borne virus. https://www.eurekalert.org/pub_releases/2019-01/uosc-usr010419.php
  3. Silvas, J. A., & Aguilar, P. V. (2017). The emergence of severe fever with thrombocytopenia syndrome virus. American Journal of Tropical Medicine and Hygiene, 97(4), 992-996.
  4. Bartíková, P., Holíková, V., Kazimírová, M., & štibrániová, I. (2017). Tick-borne viruses. Acta Virologica, 61(04), 413–427.
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