Zhang et al.
T-cell immunoglobulin and mucin domain 1 (TIM-1) is a functional entry factor for tick-borne encephalitis virus
mBio. 2022;13(1):e02860-21. doi: 10.1128/mbio.02860-21

When TBE virus attaches to receptors on the host surface membranes, the virions are taken up by receptor-mediated endocytosis. A few cell surface molecules have been suggested to play a role in virion attachment, but the host factors involved in TBE virus entry have yet to be identified. The article shows that TBE virus uses T cell immunoglobulin and mucin domain 1 (TIM-1) as a cellular entry factor and that this interaction can form a productive infection.

By an overlay binding assay of A549 cells and subsequent LC-MS/MS TIM-1 was identified as a potential receptor candidate. TIM-1 is a cell surface glycoprotein of about 100 kDa and binds to phosphatidylserine on the surface of apoptotic cells and internalizes apoptotic bodies. It serves as a receptor for several viruses through viral apoptotic mimicry.

It was shown that TBE virus particles can bind to soluble TIM-1-Fc. When TIM-1 was recombinantly expressed in the human embryonic kidney cell line 293, which normally does not express TIM1, infection rates significantly increased. Soluble TIM-1 can inhibit this binding. When A549 cells were knocked out for TIM-1, TBE virus infection was significantly reduced.

TIM-1 homozygous mice were constructed and had significantly reduced mortality when challenged with TBE virus.

It was concluded that TIM-1 is one of the factors which is responsible for TBE virus entry and TBE virus tropism.

TBE Book