Extended Data Fig. 3: 2N3R tau isoform has the lowest binding affinity to HSV1 compared to other tau isoforms.

Dilutions of synthetic tau isoforms were incubated with heat-immobilized HSV1 capsid or whole virion in an indirect ELISA to measure tau-virus binding affinity. (a) Dilutions of 2N3R tau (scale of 5 to 0.3125 μg/mL) are incubated with immobilized HSV1 capsids (F(4, 55)=33.42, *P=0.0232, ****P<0.0001). (b) Dilutions of a 50/50 mixture of 2N3R/2N4R tau (scale of 5 to 0.3125 μg/mL) are incubated with immobilized HSV1 capsids (F(4, 55)=30.21, **P=0.0071, ****P<0.0001). (c) Dilutions of 2N4R tau (scale of 5 to 0.3125 μg/mL) are incubated with immobilized HSV1 capsids (F(4, 55)=11.50, **P=0.0011, ****P<0.0001). (d) 2N4R GSK-3β p-tau binding to HSV1 was compared to 2N3R, 50/50 mix of 2N3R/2N4R, and 2N4R tau (F(3, 44)=6.913, *P=0.0211, [2N4R tau vs. 2N3R tau, **P=0.0025], [2N4R GSK-3β p-tau vs. 2N3R tau, **P=0.0012]) (e) 2N4R GSK-3β p-tau and scrambled-sequence LL-37 are incubated with immobilized HSV1 capsids (F(3, 16)=2.299, *P=0.0422, ***P=0.0002, ****P<0.0001). Box plots are representative of ±SEM (n=12) depicting median and IQR with whiskers denoting variability according to Tukey’s method. Statistical significance was calculated by one-way ANOVA using Tukey’s multiple comparisons test (a-d) and two-way ANOVA using Šídák’s multiple comparisons test (e).