Characterization and Involvement of Exosomes Originating from Chikungunya Virus-Infected Epithelial Cells in the Transmission of Infectious Viral Elements

基孔肯雅病毒感染上皮细胞的外泌体的特征及其在传染性病毒元件传播中的作用

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作者:Bao Chi Thi Le, Ati Burassakarn, Panwad Tongchai, Tipaya Ekalaksananan, Sirinart Aromseree, Supranee Phanthanawiboon, Yada Polsan, Neal Alexander, Hans J Overgaard, Chamsai Pientong

Abstract

The Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that affects the world's popula-tion with chikungunya disease. Adaptation of the viral life cycle to their host cells' environment is a key step for establishing their infection and pathogenesis. Recently, the accumulating evidence advocates a principal role of extracellular vesicles (EVs), including exosomes, in both the infection and pathogenesis of infectious diseases. However, the participation of exosomes in CHIKV infec-tion and transmission is not well clarified. Here, we demonstrated that the CHIKV RNA and pro-teins were captured in exosomes, which were released by viral-infected epithelial cells. A viral genomic element in the isolated exosomes was infectious to naïve mammalian epithelial cells. The assay of particle size distribution and transmission electron microscopy (TEM) revealed CHIKV-derived exosomes with a size range from 50 to 250 nm. Treatments with RNase A, Triton X-100, and immunoglobulin G antibodies from CHIKV-positive patient plasma indicated that in-fectious viral elements are encompassed inside the exosomes. Interestingly, our viral plaque for-mation also exhibited that infectious viral elements might be securely transmitted to neighboring cells by a secreted exosomal pathway. Taken together, our recent findings emphasize the evidence for a complementary means of CHIKV infection and suggest the role of exosome-mediated CHIKV transmission.

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