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Updated: Jul 3, 2026

Ex Vivo Infection of Murine Epidermis with Herpes Simplex Virus Type 1
Published on: August 24, 2015
Human herpesvirus-6 induces MVB formation, and virus egress occurs by an exosomal release pathway
Yasuko Mori1, Masato Koike, Eiko Moriishi
1Department of Biomedical Research, Laboratory of Virology and Vaccinology, National Institute of Biomedical Innovation, Ibaraki, Osaka, Japan. ymori@nibio.go.jp
Abstract:
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.
Insights
Human herpesvirus 6 (HHV-6) utilizes novel multivesicular body (MVB) pathways for release from T cells. Mature virions exit cells via the exosomal pathway, differing from other herpesviruses.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- The final envelopment site for most herpesviruses remains the Golgi or post-Golgi compartments.
- The specific envelopment and release pathway for human herpesvirus 6 (HHV-6) from T cells is not well-defined.
Purpose of the Study:
- To investigate the assembly and release pathways of HHV-6 in T cells.
- To elucidate the cellular compartments involved in HHV-6 maturation and egress.
Main Methods:
- Utilized electron microscopy and immunoelectron microscopy.
- Examined HHV-6-infected T cells for viral assembly sites and release mechanisms.
- Investigated the presence of viral glycoproteins and cellular markers (CD63, AP-1, TGN46) in cellular compartments.
Main Results:
- Identified novel multivesicular body (MVB)-like compartments containing mature HHV-6 virions in infected T cells.
- Observed MVB fusion with the plasma membrane and release of virions with vesicles, suggesting an exosomal pathway.
- Detected HHV-6 glycoproteins and CD63 within MVBs, on internal vesicles, and in secreted exosomes.
- Found HHV-6 budding at trans Golgi network (TGN)-associated membranes expressing CD63 and AP-1.
Conclusions:
- HHV-6 mature virions are released from T cells via multivesicular bodies (MVBs) utilizing the cellular exosomal pathway.
- This pathway differs from the typical envelopment sites of other alphaherpesviruses.
- Findings provide significant insights into the unique maturation and release mechanisms of HHV-6.
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