Human cytomegalovirus-infected cells release extracellular vesicles that carry viral surface proteins

• Published in: Virology (New York, N.Y.) Vol. 524; pp. 97 - 105
• Main Authors: Zicari, Sonia, Arakelyan, Anush, Palomino, Rogers Alberto Ñahui, Fitzgerald, Wendy, Vanpouille, Christophe, Lebedeva, Anna, Schmitt, Alain, Bomsel, Morgane, Britt, William, Margolis, Leonid
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2018; Elsevier
• Subjects: Biomarkers - analysis; Cytomegalovirus - metabolism; Cytomegalovirus Infections - virology; Extracellular vesicles; Extracellular Vesicles - metabolism; Extracellular Vesicles - virology; Genes, Reporter; HCMV; Humans; Immunology; Life Sciences; Protein Transport; rab27 GTP-Binding Proteins - analysis; Tetraspanin 30 - analysis; Triiodobenzoic Acids; Viral Matrix Proteins - metabolism; Virion; Extracellular vesicles; gH; gB; HCMV
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2018.08.008

Extracellular vesicles (EVs) released by virus-infected cells typically incorporate host and viral components inside the vesicles (cargo molecules). Here, we investigated if human cytomegalovirus (HCMV) proteins are incorporated in EV outer membrane released by HCMV-infected cells. We separated EVs from HCMV using an iodixanol step-gradient and found that the separated vesicles carried EV markers such as the tetraspanin CD63 and Rab27A. Flow analysis of individual EVs demonstrated that on average, 15 ± 3.7% of EVs were positive for gB, 5.3 ± 2.3% were positive for gH and 3.74 ± 1.5% were positive for both gB and gH. In light of previous findings demonstrating HIV envelope proteins in EV membranes, the presence of viral protein at the surface of EVs released by HCMV-infected cells indicated that viral membrane proteins incorporated in EVs released by virus-infected cells may be a general phenomenon. •Cells infected with human cytomegalovirus (HCMV) release both virions and extracellular vesicles (EVs).•EVs were separated by centrifugation on a iodixanol step-gradient and analyzed with flow cytometry.•These EVs carried typical EV markers along with HCMV envelope proteins, such as gB and gH.•Production by infected cells of EVs carrying various viral proteins is a general phenomenon for various viruses.