A null mutation in the gene encoding the herpes simplex virus type 1 UL37 polypeptide abrogates virus maturation

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• The tegument is a crucial structural component of the herpes simplex virus type 1 (HSV-1) virion.
• The UL37 open reading frame encodes a 120-kDa tegument protein essential for HSV-1 replication.

Purpose of the Study:

• To investigate the function of the UL37-encoded polypeptide in HSV-1 virion assembly and egress.
• To determine the role of UL37 in the viral maturation pathway.

Main Methods:

• Generation of a UL37 null mutant virus (KDeltaUL37) using complementing cell lines.
• Analysis of viral DNA packaging and capsid formation via sedimentation assays.
• Visualization of capsid and virion localization in infected cells using VP26-green fluorescent protein fusion.
• Ultrastructural analysis and cell fractionation to assess particle distribution and maturation stages.

Main Results:

• UL37 is essential for HSV-1 growth; KDeltaUL37 cannot replicate in nonpermissive cells.
• KDeltaUL37 forms DNA-containing capsids, indicating DNA cleavage and packaging are not dependent on UL37.
• Mutant capsids accumulate at the nuclear periphery, with impaired egress from the nucleus.
• Absence of UL37 prevents proper envelopment and egress of virions to the cytoplasm, halting the maturation pathway.

Conclusions:

• The UL37 gene product is critical for efficient capsid nuclear egress and subsequent envelopment during HSV-1 maturation.
• UL37 plays a key role in the early stages of the viral morphogenesis pathway, facilitating the formation of infectious virions.