The Rab6 post-Golgi secretory pathway contributes to herpes simplex virus 1 (HSV-1) egress.

Area of Science:

• Virology
• Cell Biology
• Microscopy

Background:

• Herpes simplex virus 1 (HSV-1) infects most of the global population, establishing lifelong latent infections.
• The mechanisms of HSV-1 intracellular transport and exocytosis are not fully understood.
• HSV-1 can cause severe disease, including encephalitis, particularly in vulnerable populations.

Purpose of the Study:

• To elucidate the late steps of HSV-1 replication, specifically the intracellular transport and exocytosis pathways.
• To investigate the role of cellular host factors in HSV-1 egress.

Main Methods:

• Development of a live-cell fluorescence microscopy assay to track individual HSV-1 virions.
• Utilized a pH-sensitive reporter to pinpoint exocytosis events.
• Investigated the involvement of the small GTPase Rab6 in HSV-1 trafficking.

Main Results:

• HSV-1 utilizes the host cell's post-Golgi secretory pathway for viral egress.
• HSV-1 particles colocalize with Rab6a, a marker of the secretory pathway, in the Golgi region.
• The virus cotraffics with Rab6a-containing vesicles to the cell periphery and undergoes exocytosis from these vesicles.
• HSV-1 accumulates at preferential egress sites, mediated by the polarized nature of the secretory pathway.

Conclusions:

• HSV-1 egress follows a pre-existing cellular secretory pathway, rather than novel virus-induced mechanisms.
• The small GTPase Rab6 plays a role in HSV-1 vesicle traffic and exocytosis.
• The findings provide insights into the late stages of the HSV-1 replication cycle.