A gamma-herpesvirus glycoprotein complex manipulates actin to promote viral spread

Area of Science:

• Virology
• Cell Biology
• Molecular Biology

Background:

• Viruses require host cell manipulation for movement within multicellular organisms.
• Herpesviruses are known for host cell manipulation, but mechanisms vary across subtypes.
• Intercellular viral spread is crucial for pathogenesis.

Purpose of the Study:

• To investigate the mechanism of intercellular spread for Murine gamma-herpesvirus-68 (MHV-68).
• To identify viral factors responsible for MHV-68-mediated cell-to-cell transmission.
• To understand how MHV-68 remodels host cell plasma membranes for virion trafficking.

Main Methods:

• Time-lapse imaging of infected cells to observe viral movement and cell surface dynamics.
• Investigating the role of MHV-68 glycoprotein gp48 and ORF58 in viral spread.
• Utilizing mutant viruses and transfected cells to assess the function of viral proteins.
• Examining the dependence on host cell actin and RhoA signaling.

Main Results:

• MHV-68 induces long, branched plasma membrane fronds, creating an intercellular network for virion transport.
• These fronds are actin-based and dependent on RhoA signaling.
• The cytoplasmic tail of gp48 is essential for plasma membrane remodeling and frond formation.
• ORF58 facilitates gp48 transport to the plasma membrane, but is not required if gp48 is correctly localized.
• The gp48/ORF58 module is sufficient to induce fronds and is conserved in Epstein-Barr virus (BDLF2/BMRF2).

Conclusions:

• MHV-68 utilizes a conserved gp48/ORF58 module to induce actin-based membrane fronds for intercellular spread.
• This mechanism enhances cell-to-cell contact and facilitates virion movement.
• Gamma-herpesviruses possess conserved strategies for manipulating host cell architecture to promote spread.