Dynamin Is Required for Efficient Cytomegalovirus Maturation and Envelopment

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Cytomegalovirus (CMV) maturation involves a virus assembly compartment (vAC) that reorganizes cellular membranes.
• Dynamin, a GTPase, is known for its role in membrane remodeling and endocytosis.
• The specific role of dynamin in viral trafficking beyond entry is not fully understood.

Purpose of the Study:

• To investigate the role of dynamin in the late stages of mouse cytomegalovirus (MCMV) infection.
• To determine if dynamin is essential for viral assembly, maturation, and envelopment.

Main Methods:

• Infection of triple dynamin knockout (TKO) mouse embryonic fibroblasts (MEFs) with MCMV.
• Analysis of viral protein expression (IE1, m04, m55/gB) at different time points.
• Ultrastructural analysis of viral maturation and envelopment.
• Treatment of MEFs with a dynamin inhibitor (dynasore).

Main Results:

• TKO cells showed reduced early viral protein IE1 but normalized levels later; however, late protein m55/gB expression was significantly reduced.
• Ultrastructural studies revealed normal nuclear viral maturation but severe defects in cytoplasmic envelopment in TKO cells.
• Dynasore treatment mimicked the TKO phenotype, confirming dynamin's role in late MCMV maturation.

Conclusions:

• Dynamin-mediated endocytic pathways are critical for the cytoplasmic stages of cytomegalovirus maturation and envelopment.
• Dynamin is dispensable for early CMV infection stages but required for efficient late-stage maturation.
• Understanding dynamin's role in CMV infection offers potential therapeutic targets for antiviral strategies.