PREPs: herpes simplex virus type 1-specific particles produced by infected cells when viral DNA replication is...

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Herpes simplex virus (HSV)-infected cells produce infectious virions and noninfectious light particles (L-particles).
• L-particles comprise envelope and tegument components but lack nucleocapsids.
• Viral DNA replication is crucial for the production of infectious HSV particles.

Purpose of the Study:

• To characterize novel virus-related particles produced during HSV DNA replication inhibition or by replication-defective mutants.
• To compare the protein composition and biological activity of these novel particles with L-particles.

Main Methods:

• Infection of BHK and MeWO cells with wild-type HSV-1 (in presence of DNA replication inhibitors) or a DNA replication-defective mutant (ambUL8).
• Analysis of released particles using electron microscopy, SDS-PAGE, and Western immunoblotting.
• Assessment of biological competence through complementation assays.

Main Results:

• A new particle type, termed pre-viral DNA replication enveloped particles (PREPs), was identified.
• PREPs exhibit altered protein composition compared to L-particles, with reduced late proteins (VP1-2, VP13/14, gC) and increased early proteins (VP4, VP11/12, VP22, gE).
• PREPs are biologically competent, delivering functional Vmw65 (VP16) and achieving 10-30% complementation efficiency.

Conclusions:

• HSV DNA replication influences the composition of non-infectious enveloped particles.
• PREPs represent a distinct class of HSV-related particles with unique protein profiles.
• PREPs retain the ability to deliver functional viral proteins, suggesting potential roles in early stages of infection.