Fig. 2: Tau binding to HSV-1 viral capsid proteins is potentiated by microtubule-binding repeats and phosphorylation.
Dilutions of synthetic tau isoforms were incubated with heat-immobilized HSV-1 capsid or whole virion in indirect and competitive ELISAs to measure tau−virus binding affinity. a, 2N4R GSK-3β p-tau binding between HSV-1 isolated capsid or whole virion was compared after normalization of available binding sites assessed using VP21/VP22a antibody (****P < 0.0001). b, Dilutions of 2N4R GSK-3β p-tau (scale of 5 µg ml−1 to 0.3125 µg ml−1) were incubated with immobilized HSV-1 capsids (F4, 55 = 43.18, ****P < 0.0001). c, The binding affinity of 2N4R GSK-3β p-tau to HSV-1 capsids was compared to 2N3R, 50/50 mix of 2N3R/2N4R and 2N4R tau (F3, 44 = 8.996, *P = 0.267 ((2N4R GSK-3β p-tau versus 2N3R tau, ***P = 0.0001), (2N4R GSK-3β p-tau versus 2N3R/2N4R tau, ***P = 0.0007)). d,e, Tau adhesion inhibition was assessed by preincubation of immobilized HSV-1 capsids with an anti-VP21/VP22a antibody (F8, 32 = 7.071, ****P < 0.0001) (d) or an anti-pUL48-VP16 antibody (F8, 32 = 3.978, ***P = 0.004, ****P < 0.0001) (e) before exposure to 2N4R GSK-3β p-tau. f, Tau adhesion inhibition was repeated with the anti-VP21/VP22a antibody using a mannose-incubated 2N4R GSK-3β p-tau. Box plots are representative of ±s.e.m. (n = 12) depicting median and interquartile range, with whiskers denoting variability according to Tukey’s method. Statistical significance was calculated by two-tailed Mann−Whitney test (a) and one-way ANOVA using Tukey’s multiple comparisons test (b−f).
