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Tick-borne Flaviviruses

Introduction

Tick-borne flaviviruses are among the medically most important arboviruses in Europe and Asia. In humans, symptoms of tick-borne flaviviruses infection range from febrile illness to more serious encephalitis and hemorrhagic complications. Tick-borne encephalitis virus (TBEV) complex which causes meningitis and encephalitis includes the following viruses: Louping ill virus (LIV), Langat virus (LGTV), Karshi virus, Powassan virus (POWV), etc. The medically most important tick-borne flavivirus is TBEV with three subtypes, the Western, the Siberian, and the Far Eastern subtype.

Virology

TBEV complex consists of single-stranded RNA viruses and is included in the genus Flavivirus. Members of the Flavivirus genus possess a single-stranded plus sense RNA genome with an average length of 11 kb, which encodes 3 structural and 7 nonstructural proteins in a single open reading frame (ORF). Infectious flavivirus particles are enveloped, smooth, spherical structures about 50 nm in diameter. The virion contains an electron-dense, 30-nm nucleocapsid which encapsulates the genomic RNA.

The flavivirus genome and translation of the viral polyprotein. Fig.1 The flavivirus genome and translation of the viral polyprotein. (Kemenesi, 2019)

TBEV Pathogenesis

After the tick bite, TBEV replicates in many host cells such as dendritic cells (DCs). DCs transport the virus to the regional lymph nodes where further replication takes place. To evade host defenses, TBEV rearranges intracellular membranes to prevent recognition of double-stranded RNA by cytoplasmic pathogen recognition receptors, allowing an approximate 24-hour delay in interferon induction. The virus ultimately penetrates the blood-brain barrier (BBB) and enters the central nervous system (CNS) where a significant amount of pathology is induced, largely as a result of the host inflammatory response. The primary targets of TBEV infection in CNS are neurons. TBEV is shown to replicate 10,000-fold higher in human neuronal cells as compared with epithelial cells.

Schematic representation of invading CNS during the TBEV infection. Fig.2 Schematic representation of invading CNS during the TBEV infection. (Palus, 2017)

Epidemiology

  • TBEV is prevalent over a wide area of the Eurasian continent including Europe, Russia, Far-Eastern Asia, and Japan. TBEV is responsible for at least 10,000 clinical cases of tick-borne encephalitis each year.
  • POWV is endemic in North America. The POWV causes encephalitis in humans and leads to long-term neurologic sequelae and death in 10% of cases.
  • LIV causes infection in sheep and grouse in the UK and causes a very rare disease in humans.
  • LGTV was isolated in Malaysia and neighboring Thailand and infects rodents, and no registered cases of human disease are associated with LGTV.

Symptoms

Usually, symptoms appear 7 to 14 days after being bitten by an infected tick. The first phase is associated with symptoms like fever, fatigue, headache, muscular ache, and nausea. In the second phase, the viruses invade the CNS which gives rise to several neurological diseases including aseptic meningitis, encephalitis, or myelitis.

What Can We offer

There is the only FDA-approved vaccine against TBEV in the United States. No POWV vaccines are available for use in humans. To better understand tick-borne flaviviruses which are associated with neuroviral disease, Creative Biolabs provides many ready-to-use antibody products and tailored antibody services to support our clients' research.

We have organized a team of excellent experts who have focused on the research of antibody development for many years. We expand our antibody services to the virology field. At present, we can provide various ViroAntibody products and services. For more detailed information, please feel free to contact us.

References

  1. Kemenesi, G.; Banyai, K. Tick-borne flaviviruses, with a focus on Powassan virus. Clin Microbiol Rev. 2019, 32(1).
  2. Palus, M.; et al, Tick-borne encephalitis virus infects human brain microvascular endothelial cells without compromising blood-brain barrier integrity. Virology. 2017, 507: 110-122.

All products and services are intended for Research Use Only, and NOT to be used in diagnostic or therapeutic procedures.

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