Structural basis for genome packaging, retention, and ejection in human cytomegalovirus

Area of Science:

• Virology
• Structural Biology
• Molecular Biology

Background:

• Human cytomegalovirus (HCMV) possesses the largest genome among human herpesviruses.
• Mechanisms of HCMV genome packaging, retention, and ejection are not fully understood.

Purpose of the Study:

• To elucidate the in situ structures of the HCMV portal and capsid vertex-specific components (CVSCs).
• To understand the roles of these structures in genome packaging, retention, and ejection.

Main Methods:

• In situ structural analysis of HCMV portal and CVSCs.
• Analysis of protein-protein interactions and conformational changes.

Main Results:

• The 5-fold symmetric 10-helix anchor of the portal interacts with DNA, potentially regulating genome packaging.
• The 6-fold symmetric turret and low-stoichiometry CVSCs contribute to genome retention.
• Conformational changes in the portal and capsid facilitate genome ejection.

Conclusions:

• The unique structural features of the HCMV portal and CVSCs are crucial for managing its large genome.
• These findings provide insights into the molecular mechanisms of herpesvirus genome manipulation.