# Langat Virus Biology and Infection

**Authors:** Zinaida Klestova, Daniel Sauter, Michael Schindler, Thomas Iftner

PMC · DOI: 10.1002/rmv.70127 · Reviews in Medical Virology · 2026-03-09

## TL;DR

This paper reviews Langat virus biology, transmission, and potential as a vaccine candidate for tick-borne flaviviruses.

## Contribution

The paper highlights LGTV's unique features and potential as a vaccine candidate, while identifying gaps in understanding its biology.

## Key findings

- LGTV can cause neurological symptoms in animal models despite often being asymptomatic in humans.
- Tick-independent transmission of LGTV in mice suggests broader transmission potential.
- Climate change may expand LGTV's geographic range through tick vector expansion.

## Abstract

Flaviviruses pose a major threat to global health and can cause severe disease in animals and humans. Among them, tick‐borne encephalitis virus (TBEV) and related members of the tick‐borne encephalitis (TBE) serocomplex are transmitted primarily by ticks and can lead to neurological disease, including encephalitis and death. Despite many years of research on the TBE‐serocomplex, no specific antiviral treatment has been developed. Langat virus (LGTV), another member of this serocomplex typically causes asymptomatic infections in humans, but may cause severe neurological disease in rare cases. Moreover, experimentally LGTV‐infected mice and monkeys show neurological symptoms. While viruses of the TBE‐serocomplex are canonically transmitted by ticks, tick‐independent transmission of LGTV has been reported in mice, suggesting a broader transmission potential. Notably, the full host range, vector competence and global distribution of LGTV remain poorly defined, and climate change‐driven expansion of tick vectors may enable the emergence of this virus in new regions. In this review, we summarise our current knowledge of LGTV, focussing on vector competence, transmission routes, tissue and host tropism, pathogenicity and animal models. Furthermore, we discuss the potential application of LGTV as a vaccine candidate for TBEV. By highlighting the unique features of LGTV and identifying current research gaps, we aim to inspire interest in this understudied virus and its value as a tool to uncover fundamental aspects of tick‐borne flavivirus biology and strategies for vaccine development.

## Linked entities

- **Diseases:** encephalitis (MONDO:0019956), neurological disease (MONDO:0005071)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** RAF1 (Raf-1 proto-oncogene, serine/threonine kinase) [NCBI Gene 5894] {aka CMD1NN, CRAF, NS5, Raf-1, c-Raf}, GSTM1 (glutathione S-transferase mu 1) [NCBI Gene 2944] {aka GST1, GSTM1-1, GSTM1a-1a, GSTM1b-1b, GTH4, GTM1}, IL6ST (interleukin 6 cytokine family signal transducer) [NCBI Gene 3572] {aka CD130, CDW130, GP130, HIES4, HIES4A, HIES4B}, HSP90AA1 (heat shock protein 90 alpha family class A member 1) [NCBI Gene 3320] {aka EL52, HEL-S-65p, HSP86, HSP89A, HSP90A, HSP90N}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, GSTK1 (glutathione S-transferase kappa 1) [NCBI Gene 373156] {aka GST, GST 13-13, GST13, GST13-13, GSTK1-1, hGSTK1}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, EIF2AK3 (eukaryotic translation initiation factor 2 alpha kinase 3) [NCBI Gene 9451] {aka PEK, PERK, WRS}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IVNS1ABP (influenza virus NS1A binding protein) [NCBI Gene 10625] {aka ARA3, FLARA3, HSPC068, IMD70, KLHL39, ND1}, IFNAR1 (interferon alpha and beta receptor subunit 1) [NCBI Gene 3454] {aka AVP, CRF2-1, IFN-R-1, IFN-alpha-REC, IFNAR, IFNBR}, HSPA4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 3308] {aka APG-2, HEL-S-5a, HS24/P52, HSPH2, RY, hsp70}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, HSP90B1 (heat shock protein 90 beta family member 1) [NCBI Gene 7184] {aka ECGP, GP96, GRP94, HEL-S-125m, HEL35, TRA1}
- **Diseases:** neurological disease (MESH:D020271), neuronal damage (MESH:D009410), gait disturbance (MESH:D020233), myalgia (MESH:D063806), paralysis (MESH:D010243), Impaired learning and memory formation (MESH:D007859), tick-borne flavivirus infections (MESH:D018177), TBE (MESH:D004675), neuroblastoma (MESH:D009447), neurological dysfunction (MESH:D009461), LGTV encephalitis (MESH:D018792), memory deficits (MESH:D008569), neurological sequelae (MESH:D009422), astrogliosis (MESH:D005911), neuropathological changes (MESH:C000723354), neurological lesions (MESH:D019636), inflammation (MESH:D007249), headache (MESH:D006261), colon cancer (MESH:D015179), LGTV (MESH:D014777), intracerebral infection (MESH:D002543), hypokinesia (MESH:D018476), leukemia (MESH:D007938), flu (MESH:D007251), meningoencephalitis (MESH:D008590), death (MESH:D003643), cancer (MESH:D009369), encephalitis (MESH:D004660), Infection (MESH:D007239), meningitis (MESH:D008580), neurological complications (MESH:D002493), anxiety (MESH:D001007), weight loss (MESH:D015431)
- **Chemicals:** 5-fluorouracil (MESH:D005472), TP21 (MESH:D013881), lipid (MESH:D008055), glycolipids (MESH:D006017), formalin (MESH:D005557), Elantcev 15-20/3 (-), HS (MESH:D006497), gangliosides (MESH:D005732), glycan (MESH:D011134)
- **Species:** Ixodes persulcatus (taiga tick, species) [taxon 34615], Tick-borne encephalitis virus (no rank) [taxon 11084], Ovis aries (domestic sheep, species) [taxon 9940], Sundamys muelleri (Mueller's giant Sunda rat, species) [taxon 83761], Haemaphysalis longicornis (longhorned tick, species) [taxon 44386], Crunomys rajah (Rajah spiny rat, species) [taxon 907928], Semliki Forest virus (no rank) [taxon 11033], Gallus gallus (bantam, species) [taxon 9031], Flavivirus [taxon 11051], Ixodes granulatus (species) [taxon 59647], Capra hircus (domestic goat, species) [taxon 9925], Sindbis virus (no rank) [taxon 11034], Ixodes scapularis (blacklegged tick, species) [taxon 6945], Alkhumra hemorrhagic fever virus (no rank) [taxon 172148], Berylmys bowersi (Bower's white-toothed rat, species) [taxon 83759], Ixodes ricinus (castor bean tick, species) [taxon 34613], Kyasanur Forest disease virus (no rank) [taxon 33743], dengue virus type 4 (no rank) [taxon 11070], Cercopithecidae (monkey, family) [taxon 9527], Mus musculus (house mouse, species) [taxon 10090], Powassan virus (no rank) [taxon 11083], Tubbia sp. (be) (species) [taxon 2579439], Rattus norvegicus (brown rat, species) [taxon 10116], Louping ill virus (no rank) [taxon 11086], Langat virus (no rank) [taxon 11085], Homo sapiens (human, species) [taxon 9606], Ornithodoros sonrai (species) [taxon 352064], Omsk hemorrhagic fever virus (no rank) [taxon 12542]
- **Mutations:** A2G
- **Cell lines:** /6 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_5985), Vero — Chlorocebus sabaeus (Green monkey), Spontaneously immortalized cell line (CVCL_0059), ISE6 — Ixodes scapularis (Black-legged tick), Spontaneously immortalized cell line (CVCL_Z170), TP21 — Oryctolagus cuniculus (Rabbit), Transformed cell line (CVCL_J968), SW620 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0547), E5-104 — Homo sapiens (Human), Transformed cell line (CVCL_N203), NCI60 — Homo sapiens (Human), Lung small cell carcinoma, Cancer cell line (CVCL_A592), HEK293T — Homo sapiens (Human), Transformed cell line (CVCL_0063), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023)

## Full text

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## Figures

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## References

96 references — full list in the complete paper: https://tomesphere.com/paper/PMC12972639/full.md

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Source: https://tomesphere.com/paper/PMC12972639