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

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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