Extracellular vesicles from KSHV-infected endothelial cells activate the complement system
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Hyungtaek Jeon1, Seung-Min Yoo1, Hyo Sun Choi2, Ji Young Mun2,3, Hee-Gyoo Kang3, Jiyeong Lee3, Jinsung Park4, Shou-Jiang Gao5 and Myung-Shin Lee1
1Department of Microbiology and Immunology, Eulji University School of Medicine, Daejeon, South Korea
2BK21 Plus Program, Department of Senior Healthcare, Graduate School, Eulji University, Daejeon, South Korea
3Department of Biomedical Laboratory Science, College of Health Sciences, Eulji University, Gyeonggi-Do, Seongnam, South Korea
4Department of Urology, Eulji University School of Medicine, Daejeon, South Korea
5Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Myung-Shin Lee, email: firstname.lastname@example.org
Shou-Jiang Gao, email: email@example.com
Keywords: extracellular vesicles, KSHV, complement system, alternative complement pathway, endothelial cells
Received: August 18, 2017 Accepted: September 20, 2017 Published: October 09, 2017
Extracellular vesicles (EVs), released by cells, are associated with cell-to-cell communication and regulate various cellular processes. EVs draw parallels with viruses for their similar structures and functions. Increasing evidences from recent studies indicate that cells infected with viruses release a variety of EVs. Delineating the functions and mechanisms of EVs released during virus infection is essential for understanding the molecular basis of viral infection and replication as well as associated pathogenesis. The most challenging obstacle for these studies is the separation of EVs from viruses. In this study, we successfully isolated the EVs from de novo Kaposi’s sarcoma-associated herpesvirus (KSHV) infected-human endothelial cells during the period between virus entry and production. Intriguingly, a proteomics analysis of these EVs has revealed alterations of the complement system. Additionally, we have discovered that the EVs from KSHV-infected endothelial cells are potent activators of an alternative pathway of the complement system via exploitation of the endogenous C3 complement protein and properdin. Furthermore, we have found that complement activation promotes KSHV persistent latent infection by activating the NF-κB pathway, which enhances the survival of KSHV-infected cells and inhibits viral lytic replication. Our work identifies a novel role of EVs induced by KSHV during de novo infection and the underlying mechanism of complement activation by EVs.
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