PMID- 18637904 OWN - NLM STAT- MEDLINE DCOM- 20090113 LR - 20211020 IS - 1600-0854 (Electronic) IS - 1398-9219 (Print) IS - 1398-9219 (Linking) VI - 9 IP - 10 DP - 2008 Sep TI - Human herpesvirus-6 induces MVB formation, and virus egress occurs by an exosomal release pathway. PG - 1728-42 LID - 10.1111/j.1600-0854.2008.00796.x [doi] AB - The final envelopment of most herpesviruses occurs at Golgi or post-Golgi compartments, such as the trans Golgi network (TGN); however, the final envelopment site of human herpesvirus 6 (HHV-6) is uncertain. In this study, we found novel pathways for HHV-6 assembly and release from T cells that differed, in part, from those of alphaherpesviruses. Electron microscopy showed that late in infection, HHV-6-infected cells were larger than uninfected cells and contained many newly formed multivesicular body (MVB)-like compartments that included small vesicles. These MVBs surrounded the Golgi apparatus. Mature virions were found in the MVBs and MVB fusion with plasma membrane, and the release of mature virions together with small vesicles was observed at the cell surface. Immunoelectron microscopy demonstrated that the MVBs contained CD63, an MVB/late endosome marker, and HHV-6 envelope glycoproteins. The viral glycoproteins also localized to internal vesicles in the MVBs and to secreted vesicles (exosomes). Furthermore, we found virus budding at TGN-associated membranes, which expressed CD63, adaptor protein (AP-1) and TGN46, and CD63 incorporation into virions. Our findings suggest that mature HHV-6 virions are released together with internal vesicles through MVBs by the cellular exosomal pathway. This scenario has significant implications for understanding HHV-6's maturation pathway. FAU - Mori, Yasuko AU - Mori Y AD - Department of Biomedical Research, Laboratory of Virology and Vaccinology, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan. ymori@nibio.go.jp FAU - Koike, Masato AU - Koike M FAU - Moriishi, Eiko AU - Moriishi E FAU - Kawabata, Akiko AU - Kawabata A FAU - Tang, Huamin AU - Tang H FAU - Oyaizu, Hiroko AU - Oyaizu H FAU - Uchiyama, Yasuo AU - Uchiyama Y FAU - Yamanishi, Koichi AU - Yamanishi K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080711 PL - England TA - Traffic JT - Traffic (Copenhagen, Denmark) JID - 100939340 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (CD63 protein, human) RN - 0 (Platelet Membrane Glycoproteins) RN - 0 (Tetraspanin 30) RN - 0 (Viral Envelope Proteins) SB - IM MH - Antibodies, Monoclonal MH - Antigens, CD/metabolism MH - Cell Line MH - Cell Membrane/metabolism/ultrastructure/virology MH - Endosomes/metabolism/ultrastructure/*virology MH - Exosomes/metabolism/ultrastructure/virology MH - Golgi Apparatus/metabolism/ultrastructure/virology MH - Herpesvirus 6, Human/immunology/metabolism/*physiology/ultrastructure MH - Humans MH - Immunoprecipitation MH - Microscopy, Immunoelectron MH - Platelet Membrane Glycoproteins/metabolism MH - Tetraspanin 30 MH - Viral Envelope Proteins/metabolism MH - Virion/metabolism/physiology/ultrastructure MH - Virus Assembly/*physiology PMC - PMC2613231 EDAT- 2008/07/22 09:00 MHDA- 2009/01/14 09:00 PMCR- 2009/01/02 CRDT- 2008/07/22 09:00 PHST- 2008/07/22 09:00 [pubmed] PHST- 2009/01/14 09:00 [medline] PHST- 2008/07/22 09:00 [entrez] PHST- 2009/01/02 00:00 [pmc-release] AID - TRA796 [pii] AID - 10.1111/j.1600-0854.2008.00796.x [doi] PST - ppublish SO - Traffic. 2008 Sep;9(10):1728-42. doi: 10.1111/j.1600-0854.2008.00796.x. Epub 2008 Jul 11.