Exosomes collected from Akata-LCLs accelerate LPD formation. (A) Electron microscope image of exosomes isolated from Akata-LCL (left) and B95-8-LCL culture medium by ultracentrifugation. Scale bar, 100 nm. (B) Survival curve of B95-8/miRNA-rich exosome-treated mice (n = 8, solid line) or B95-8/EBV-miRNA-deleted exosomes-treated mice (n = 5, dashed line). P = .01, log-rank test. (C) The spleens were stained with hematoxylin and eosin or treated for EBER in situ hybridization. Scale bar, 50 μm. (D) CD68 and CD163 immunohistochemical staining of the spleen (left). Scale bar, 50 μm. The cells positive for each macrophage marker were counted (right). Two mice were treated per group, and 3 fields were counted in each mouse. *P < .01, Student t test. (E, left top) qPCR revealed that the B95-8 virus-specific region was amplified in LPD in B95-8/miRNA-rich exosome-treated mice. (Left bottom) Akata virus-specific region was not amplified. (Right) The binding sites of primer pairs used to specifically amplify the B95-8 virus genome and Akata virus genome are indicated. Indicated primer pair detects B95-8 genome (top) and Akata genome (bottom), respectively. Half of the BART cluster 1 miRNAs, and all BART cluster 2 miRNAs were deleted in the B95-8, but not in Akata virus.