Correlation of Severity of Human Tick-Borne Encephalitis Virus Disease and Pathogenicity in Mice

Kurhade, Chaitanya; Schreier, Sarah; Lee, Yi Ping; Zegenhagen, Loreen; Hjertqvist, Marika; Dobler, Gerhard; Kröger, Andrea; Överby, Anna K.

doi:10.3201/eid2409.171825

Cited by 15 publications

(9 citation statements)

References 16 publications

(17 reference statements)

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“…A number of hematophagous arthropods feed on bats, including bat flies (genera Nycteribiidae and Streblidae ), bat bugs and bed bugs (family Cimicidae ), and ticks (families Argasidae and Ixodidae ) [18,20,21,167,168,169,170,171,172]. Viruses of medical and veterinary significance have also been isolated from these arthropods [21,173,174,175]. However, the contribution that these ectoparasites play in the circulation of medically important viruses among bats and other hosts is unclear and necessitates further investigation.…”

Section: Relationships Between Bats and Arthropodsmentioning

confidence: 99%

Can Bats Serve as Reservoirs for Arboviruses?

Fagre

Kading

2019

Viruses

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Bats are known to harbor and transmit many emerging and re-emerging viruses, many of which are extremely pathogenic in humans but do not cause overt pathology in their bat reservoir hosts: henipaviruses (Nipah and Hendra), filoviruses (Ebola and Marburg), and coronaviruses (SARS-CoV and MERS-CoV). Direct transmission cycles are often implicated in these outbreaks, with virus shed in bat feces, urine, and saliva. An additional mode of virus transmission between bats and humans requiring further exploration is the spread of disease via arthropod vectors. Despite the shared ecological niches that bats fill with many hematophagous arthropods (e.g. mosquitoes, ticks, biting midges, etc.) known to play a role in the transmission of medically important arboviruses, knowledge surrounding the potential for bats to act as reservoirs for arboviruses is limited. To this end, a comprehensive literature review was undertaken examining the current understanding and potential for bats to act as reservoirs for viruses transmitted by blood-feeding arthropods. Serosurveillance and viral isolation from either free-ranging or captive bats are described in relation to four arboviral groups (Bunyavirales, Flaviviridae, Reoviridae, Togaviridae). Further, ecological associations between bats and hematophagous viral vectors are characterized (e.g. bat bloodmeals in mosquitoes, ingestion of mosquitoes by bats, etc). Lastly, knowledge gaps related to hematophagous ectoparasites (bat bugs and bed bugs (Cimicidae) and bat flies (Nycteribiidae and Streblidae)), in addition to future directions for characterization of bat-vector-virus relationships are described.

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Section: Relationships Between Bats and Arthropodsmentioning

confidence: 99%

Can Bats Serve as Reservoirs for Arboviruses?

Fagre

Kading

2019

Viruses

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“…Though, the castor bean tick ( Ixodes ricinus ) is the most common tick species in Europe and considered as the major vector of the European TBE virus (Chitimia‐Dobler et al, 2019). Different subtypes of the virus are circulating within different geographical areas, and these may be associated with different severity of disease (Kurhade et al, 2018). The virus is widespread, and five known subtypes have been detected: the European (TBEV‐Eu), Siberian (TBEV‐Sib), Far Eastern (TBEV‐Fe), Himalayan (TBEV‐Him) and Baikalian (TBEV‐Bkl) (Dai, Shang, Lu, Yang, & Xu, 2018; Kovalev & Mukhacheva, 2017).…”

Section: Introductionmentioning

confidence: 99%

Geographical distribution and prevalence of tick‐borne encephalitis virus in questing Ixodes ricinus ticks and phylogeographic structure of the Ixodes ricinus vector in Norway

Vikse

Paulsen

Edgar

et al. 2020

Zoonoses and Public Health

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The tick-borne encephalitis virus (TBEV), a zoonotic flaviviral infection, is endemic in large parts of Norway and Eurasia. Humans are mainly infected with TBEV via bites from infected ticks. In Norway, the main geographical distribution of ticks is along the Norwegian coastline from southeast (~59°N) and up to the southern parts of Nordland County (~65°N). In this study, we collected ticks by flagging along the coast from Østfold County to Nordland County. By whole-genome sequencing of the mitochondrial genome of Ixodes ricinus, the phylogenetic tree suggests that there is limited phylogeographic structure both in Norway and in Europe. The overall TBEV prevalence is 0.3% for nymphs and 4.3% for adults. The highest estimated TBEV prevalence in adult ticks was detected in Rogaland and Vestfold County, while for nymphs it is highest in Vestfold, Vest-Agder and Rogaland. The present work is one of the largest studies on distribution and prevalence of TBEV in ticks in Scandinavia, showing that the virus is wider distributed in Norway than previously anticipated. K E Y W O R D Sgeographical distribution, Ixodes ricinus, phylogeography, prevalence, TBEV, WGS | 371 VIKSE Et al.

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“…The symptoms of a TBEV infection range from a subclinical form to a mild febrile illness, to meningitis and encephalitis. The exact determinants of the disease severity are not known; however, infectious dose, age, genotype, and immune status of the host as well as the virulence of the virus strain are thought to play a role [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

The envelope protein of tick-borne encephalitis virus influences neuron entry, pathogenicity, and vaccine protection

Lindqvist

Rosendal

Weber

et al. 2020

J Neuroinflammation

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Background Tick-borne encephalitis virus (TBEV) is considered to be the medically most important arthropod-borne virus in Europe. The symptoms of an infection range from subclinical to mild flu-like disease to lethal encephalitis. The exact determinants of disease severity are not known; however, the virulence of the strain as well as the immune status of the host are thought to be important factors for the outcome of the infection. Here we investigated virulence determinants in TBEV infection. Method Mice were infected with different TBEV strains, and high virulent and low virulent TBEV strains were chosen. Sequence alignment identified differences that were cloned to generate chimera virus. The infection rate of the parental and chimeric virus were evaluated in primary mouse neurons, astrocytes, mouse embryonic fibroblasts, and in vivo. Neutralizing capacity of serum from individuals vaccinated with the FSME-IMMUN® and Encepur® or combined were evaluated. Results We identified a highly pathogenic and neurovirulent TBEV strain, 93/783. Using sequence analysis, we identified the envelope (E) protein of 93/783 as a potential virulence determinant and cloned it into the less pathogenic TBEV strain Torö. We found that the chimeric virus specifically infected primary neurons more efficiently compared to wild-type (WT) Torö and this correlated with enhanced pathogenicity and higher levels of viral RNA in vivo. The E protein is also the major target of neutralizing antibodies; thus, genetic variation in the E protein could influence the efficiency of the two available vaccines, FSME-IMMUN® and Encepur®. As TBEV vaccine breakthroughs have occurred in Europe, we chose to compare neutralizing capacity from individuals vaccinated with the two different vaccines or a combination of them. Our data suggest that the different vaccines do not perform equally well against the two Swedish strains. Conclusions Our findings show that two amino acid substitutions of the E protein found in 93/783, A83T, and A463S enhanced Torö infection of neurons as well as pathogenesis and viral replication in vivo; furthermore, we found that genetic divergence from the vaccine strain resulted in lower neutralizing antibody titers in vaccinated individuals.

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Correlation of Severity of Human Tick-Borne Encephalitis Virus Disease and Pathogenicity in Mice

Cited by 15 publications

References 16 publications

Can Bats Serve as Reservoirs for Arboviruses?

Can Bats Serve as Reservoirs for Arboviruses?

Geographical distribution and prevalence of tick‐borne encephalitis virus in questing Ixodes ricinus ticks and phylogeographic structure of the Ixodes ricinus vector in Norway

The envelope protein of tick-borne encephalitis virus influences neuron entry, pathogenicity, and vaccine protection

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