Structural rearrangement within an enveloped virus upon binding to the host cell

Area of Science:

• Virology
• Molecular Biology
• Cellular Biology

Background:

• Viruses are known to trigger host signaling pathways upon cell surface receptor binding.
• However, evidence for a reverse signaling pathway, from the exterior to the interior of a virus, has been lacking.
• The herpes simplex virus tegument, located between the viral envelope and capsid, is crucial for viral structure and function.

Purpose of the Study:

• To investigate the potential for "outside-in" signaling across the viral envelope of herpes simplex virus.
• To identify the molecular mechanisms underlying structural changes in the viral tegument upon receptor interaction.
• To explore the role of the tegument protein UL16 in this signaling process.

Main Methods:

• Studying the interaction of herpes simplex virus virions with cell attachment receptors at low temperatures (4°C).
• Utilizing N-ethylmaleimide to stabilize the interaction between the tegument protein UL16 and viral capsids.
• Employing NP-40 to disrupt virions and isolate capsid-UL16 complexes.
• Investigating binding to immobilized heparin and the role of viral glycoprotein C.

Main Results:

• Herpes simplex virus binding to cell receptors induces rapid and efficient structural changes in the viral tegument.
• The interaction of UL16 with viral capsids, normally destabilized during egress, can be restabilized by N-ethylmaleimide.
• Viral binding to cells or immobilized heparin triggers the release of UL16 from capsids, indicating "outside-in" signaling.
• This signaling process requires viral glycoprotein C when binding to heparin.

Conclusions:

• Herpes simplex virus exhibits "outside-in" signaling across its envelope upon receptor binding.
• This represents the first documented instance of signaling across a viral envelope initiated by receptor engagement.
• The structural changes in the tegument are a direct consequence of this newly identified viral signaling mechanism.