August 15, 2025Open Access

Interactions between tick-borne encephalitis virus non-structural protein 1 and blood-brain barrier tight junction proteins: potential clues to strain-specific neuropathogenicity

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Discussion

Investigation of NS1 interactions with tight junction proteins reveals strain-specific pathways for neuroinvasion.

Higher predicted interactions of NS1 from the highly pathogenic Hypr strain with multiple tight junction proteins, indicating potential pathways for neuroinvasion.
Experimental validation showed Hypr NS1 had a high-affinity binding (KD = 0.271 ug/mL) to JAM-A, unlike the low pathogenic strain Vs, indicating strain-specific binding profiles.
Utilizing AlphaFold3 multimer modeling and in vitro binding assays enables detailed understanding of blood-brain barrier interactions.
Differential interactions hint at neuroinvasive pathways that may contribute to chronic neurological disease from the lower pathogenic strain, warranting further exploration.

Goonawardane et al. (2025) studied this question.

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