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A virus resembling Russian spring-summer encephalitis virus from an ixodid tick in Malaya

SMITH CE

Nature, 1956 Sep 15;178(4533):581-2.
PMID: 13369466
Matched MeSH terms: Encephalitis, Tick-Borne*
NS3 protease of Langat tick-borne flavivirus cleaves serine protease substrates

Scaramozzino N, Crance JM, Drouet C, Roebuck JP, Drouet E, Jouan A, et al.

Biochem Biophys Res Commun, 2002 May 31;294(1):16-22.
PMID: 12054734

Langat (LGT) virus, initially isolated in 1956 from ticks in Malaysia, is a naturally occurring nonpathogenic virus with a very close antigenicity to the highly pathogenic tick-borne encephalitis (TBE) Western subtype virus and TBE Far Eastern subtype virus. NS3, the second largest viral protein of LGT virus, is highly conserved among flaviviruses and contains a characteristic protease moiety (NS3 pro). NS3 pro represents an attractive target for anti-protease molecules against TBE virus. We report herein a purification method specially designed for NS3 pro of LGT using a strategy for proper refolding coupled with the enzymatic characterisation of the protein. Different p-nitroanilide substrates, defined on canonic sequences for their susceptibility to Ser-protease, were applied to the proteolytic assays of the protein. The highest values were obtained from substrates containing an Arg or Lys (amino acid) residue at the P1 position. This purification method will facilitate the future development of reliable testing procedures for anti-proteases directed to NS3 proteins.

Matched MeSH terms: Encephalitis, Tick-Borne/enzymology; Encephalitis, Tick-Borne/virology
Fulltext Geographic distribution of Tick-borne encephalitis virus complex

Im JH, Baek JH, Durey A, Kwon HY, Chung MH, Lee JS

J Vector Borne Dis, 2020 1 1;57(1):14-22.
PMID: 33818450 DOI: 10.4103/0972-9062.308794

A comprehensive understanding of the geographic distribution of the tick-borne encephalitis virus (TBEV) complex is necessary due to increasing transboundary movement and cross-reactivity of serological tests. This review was conducted to identify the geographic distribution of the TBEV complex, including TBE virus, Alkhurma haemorrhagic fever virus, Kyasanur forest disease virus, louping-ill virus, Omsk haemorrhagic fever virus, and Powassan virus. Published reports were identified using PubMed, EMBASE, and the Cochrane library. In addition to TBEV complex case-related studies, seroprevalence studies were also retrieved to assess the risk of TBEV complex infection. Among 1406 search results, 314 articles met the inclusion criteria. The following countries, which are known to TBEV epidemic region, had conducted national surveillance studies: Austria, China, Czech, Denmark, Estonia, Finland, Germany, Hungary, Italy, Latvia, Norway, Poland, Romania, Russia, Switzerland, Sweden, Slovenia, and Slovakia. There were also studies/reports on human TBEV infection from Belarus, Bulgaria, Croatia, France, Japan, Kyrgyzstan, Netherland, and Turkey. Seroprevalence studies were found in some areas far from the TBEV belt, specifically Malaysia, Comoros, Djibouti, and Kenya. Kyasanur forest disease virus was reported in southwestern India and Yunnan of China, the Powassan virus in the United States, Canada, and east Siberia, Alkhurma haemorrhagic fever virus in Saudi Arabia and east Egypt, and Louping-ill virus in the United Kingdom, Ireland, and east Siberia. In some areas, the distribution of the TBEV complex overlaps with that of other viruses, and caution is recommended during serologic diagnosis. The geographic distribution of the TBEV complex appears to be wide and overlap of the TBE virus complex with other viruses was observed in some areas. Knowledge of the geographical distribution of the TBEV complex could help avoid cross-reactivity during the serologic diagnosis of these viruses. Surveillance studies can implement effective control measures according to the distribution pattern of these viruses.

Matched MeSH terms: Encephalitis, Tick-Borne/immunology; Encephalitis, Tick-Borne/epidemiology*
Fulltext Cerebral glucose hypometabolism in Tick-Borne Encephalitis, a pilot study in 10 Patients

Dietmann A, Putzer D, Beer R, Helbok R, Pfausler B, Nordin AJ, et al.

Int J Infect Dis, 2016 Oct;51:73-77.
PMID: 27418580 DOI: 10.1016/j.ijid.2016.06.022

BACKGROUND: Tick borne encephalitis (TBE) is an acute meningoencephalitis with or without myelitis caused by an RNA virus from the flavivirus family transmitted by Ixodes spp ticks. The neurotropic TBE virus infects preferentially large neurons in basal ganglia, anterior horns, medulla oblongata, Purkinje cells and thalamus. Brain metabolic changes related to radiologic and clinical findings have not been described so far.
METHODS: Here we describe the clinical course of 10 consecutive TBE patients with outcome assessment at discharge and after 12 month using a modified Rankin Scale. Patients underwent cerebral MRI after confirmation of diagnosis and before discharge. (18)F-FDG PET/CT scans were performed within day 5 to day 14 after TBE diagnosis. Extended analysis of coagulation parameters by thrombelastometry (ROTEM® InTEM, ExTEM, FibTEM) was performed every other day after confirmation of TBE diagnosis up to day 10 after hospital admission or discharge.
RESULTS: All patients presented with a meningoencephalitic course of disease. Cerebral MRI scans showed unspecific findings at predilection areas in 3 patients. (18)F-FDG PET/CT showed increased glucose utilization in one patient and decreased (18)F-FDG uptake in seven patients. Changes in coagulation measured by standard parameters and thrombelastometry were not found in any of the patients.
DISCUSSION: Glucose hypometabolism was present in 7 out of 10 TBE patients reflecting neuronal dysfunction in predilection areas of TBE virus infiltration responsible for development of clinical signs and symptoms.

Matched MeSH terms: Encephalitis, Tick-Borne/metabolism*; Encephalitis, Tick-Borne/virology
Innate and adaptive immunity in wild rodents spontaneously and experimentally infected with the tick-borne encephalitis virus

Morozova OV, Panov VV, Bakhvalova VN

Infect Genet Evol, 2020 Jun;80:104187.
PMID: 31927073 DOI: 10.1016/j.meegid.2020.104187

Two dominant species of wild small rodents trapped in Novosibirsk region, South-Western Siberia, Russia differed in their susceptibility to the tick-borne encephalitis virus (TBEV) infection. TBEV RNA average detection rate for Northern red-backed vole Myodes rutilus (Pallas, 1779) (82.2 ± 5.8% blood samples and 63.1 ± 2.7% organ samples) significantly exceeded the corresponding values for the striped field mouse Apodemus agrarius (Pallas, 1771) (47.0 ± 8.7% blood and 24.5 ± 2.8% organ samples) (p <0.001). Innate immunity may be one of possible reasons of the differences. Th1 cytokine gene expression distinguished between M. rutilus (12.5 ± 8.5%) and A. agrarius (66.6 ± 11.4%), whereas Th2 cytokine frequencies were statistically similar (81.8 ± 12.2% and 100.0%, respectively). Polarization indexes (PI) of the innate immunity calculated as ratio of Th2 to Th1 cytokine RNA detection rates for both M. rutilus (6.5) and A. agrarius (1.5) suggested Th2 mainly humoral immune response against persistent TBEV in natural mammalian hosts. Therefore, the TBEV-induced antibodies were analyzed by ELISA and hemagglutination inhibition (HI) tests. The TBEV-specific antibodies were detected in 74.8 ± 4.3% sera of M. rutilus and 67.3 ± 6.8% of A. agrarius. Among them HI antibodies were found in 4.8 ± 2.1% of the same analyzed sera of M. rutilus and in 6.0 ± 3.4% blood samples of A. agrarius only. To model the TBEV persistence both M. rutilus and A. agrarius were infected with the suspensions of the TBEV-infected ticks with further observations during 4 subsequent months. Detection rate of the TBEV RNA and antigen E remained high during the whole period, however, pathogenic for laboratory suckling mice virus was isolated up to 8 days postinfection. At late stages of the persistent infection (1-4 months) the TBEV RNA detection rate in northern red-backed voles remained high 70.6 ± 7.9% whereas in striped field mice significantly declined to 26.7 ± 9.2% (p .05) but Th1 cytokine mRNA detection rates were different (44.4 ± 12.5% and 85.7 ± 9.7%, respectively) (p

Matched MeSH terms: Encephalitis, Tick-Borne/veterinary*
Infectious cDNA clone of attenuated Langat tick-borne flavivirus (strain E5) and a 3' deletion mutant constructed from it exhibit decreased neuroinvasiveness in immunodeficient mice

Pletnev AG

Virology, 2001 Apr 10;282(2):288-300.
PMID: 11289811

Forty-five years ago a naturally attenuated tick-borne flavivirus, Langat (LGT) strain TP21, was recovered from ticks in Malaysia. Subsequently, it was tested as a live attenuated vaccine for virulent tick-borne encephalitis viruses. In a large clinical trial its attenuation was confirmed but there was evidence of a low level of residual virulence. Thirty-five years ago further attenuation of LGT TP21 was achieved by multiple passages in eggs to yield mutant E5. To study the genetic determinants of the further attenuation exhibited by E5 and to allow us to manipulate the genome of this virus for the purpose of developing a satisfactory live attenuated tick-borne flavivirus vaccine, we recovered infectious E5 virus from a full-length cDNA clone. The recombinant E5 virus (clone 651) recovered from a full-length infectious cDNA clone was more attenuated in immunodeficient mice than that of its biologically derived E5 parent. Increase in attenuation was associated with three amino acid substitutions, two located in the structural protein E and one in nonstructural protein NS4B. Subsequently an even greater degree of attenuation was achieved by creating a viable 320 nucleotide deletion in the 3'-noncoding region of infectious full-length E5 cDNA. This deletion mutant was not cytopathic in simian Vero cells and it replicated to lower titer than its E5-651 parent. In addition, the E5 3' deletion mutant was less neuroinvasive in SCID mice than its E5-651 parent. Significantly, the deletion mutant proved to be 119,750 times less neuroinvasive in SCID mice than its progenitor, LGT strain TP21. Despite its high level of attenuation, the E5 3' deletion mutant remained highly immunogenic and intraperitoneal (ip) inoculation of 10 PFU induced complete protection in Swiss mice against subsequent challenge with 2000 ip LD50 of the wild-type LGT TP21.

Matched MeSH terms: Encephalitis, Tick-Borne/immunology; Encephalitis, Tick-Borne/pathology; Encephalitis, Tick-Borne/prevention & control; Encephalitis, Tick-Borne/virology
Fulltext Detection of Langat virus by TaqMan real-time one-step qRT-PCR method

Muhd Radzi SF, Rückert C, Sam SS, Teoh BT, Jee PF, Phoon WH, et al.

Sci Rep, 2015;5:14007.
PMID: 26360297 DOI: 10.1038/srep14007

Langat virus (LGTV), one of the members of the tick-borne encephalitis virus (TBEV) complex, was firstly isolated from Ixodes granulatus ticks in Malaysia. However, the prevalence of LGTV in ticks in the region remains unknown. Surveillance for LGTV is therefore important and thus a tool for specific detection of LGTV is needed. In the present study, we developed a real-time quantitative reverse-transcription-polymerase chain reaction (qRT-PCR) for rapid detection of LGTV. Our findings showed that the developed qRT-PCR could detect LGTV at a titre as low as 0.1 FFU/ml. The detection limit of the qRT-PCR assay at 95% probability was 0.28 FFU/ml as determined by probit analysis (p ≤ 0.05). Besides, the designed primers and probe did not amplify ORF of the E genes for some closely related and more pathogenic viruses including TBEV, Louping ill virus, Omsk hemorrhagic fever virus (OHFV), Alkhurma virus (ALKV), Kyasanur Forest Disease virus (KFDV) and Powassan virus (POWV) which showed the acceptable specificity of the developed assay. The sensitivity of the developed method also has been confirmed by determining the LGTV in infected tick cell line as well as LGTV- spiked tick tissues.

Matched MeSH terms: Encephalitis, Tick-Borne
Fulltext Serological screening of Tick-borne encephalitis (TBE) among Malaysian encephalitis patients

Thayan R, Khairullah NS, Ho TM

Trop Biomed, 2004 Dec;21(2):153-6.
PMID: 16493408

Tick-borne encephalitis (TBE) is a viral infection of the central nervous system and is caused by tick bites, usually after travel to rural or forested areas. The disease is prevalent in Scandinavia, Western Europe, Central Europe and the former Soviet Union and East Asia including Japan. In Malaysia, so far there are no reported cases of TBE. In the present time, many illnesses have been attributed to traveling to other parts of the world. Thus it is important to carry out TBE prevalence study to determine whether the virus is present among Malaysian population. Samples (sera and CSF) from patients admitted to major MOH hospitals in Peninsular Malaysia and Sabah with a clinical diagnosis of encephalitis but is IgM negative for JE, were tested for TBEV IgM ELISA and TBEV IgG ELISA (DRG, Germany). Out of the 600 samples screened for TBEV IgG, all were non-reactive. In addition, out of the 100 samples screened for TBEV IgM, all the samples were also non-reactive. Our results indicate that currently TBE is not present in the Malaysian population. Among the reasons for this could be lack of the infection agent, absence of the suitable vector or subjects selected for the study did not fit the criteria of possible exposure to TBE infections. Hence we recommend that for any future study, the selection of subjects should include those who returned from tick-infested forested areas.

Matched MeSH terms: Encephalitis, Tick-Borne