Tegument Assembly, Secondary Envelopment and Exocytosis.

Ian B Hogue

doi:10.21775/cimb.042.551

Abstract

Alphaherpesvirus tegument assembly, secondary envelopment, and exocytosis processes are understood in broad strokes, but many of the individual steps in this pathway, and their molecular and cell biological details, remain unclear. Viral tegument and membrane proteins form an extensive and robust protein interaction network, such that essentially any structural protein can be deleted, yet particles are still assembled, enveloped, and released from infected cells. We conceptually divide the tegument proteins into three groups: conserved inner and outer teguments that participate in nucleocapsid and membrane contacts, respectively; and 'middle' tegument proteins, consisting of some of the most abundant tegument proteins that serve as central hubs in the protein interaction network, yet which are unique to the alphaherpesviruses. We then discuss secondary envelopment, reviewing the tegument-membrane contacts and cellular factors that drive this process. We place this viral process in the context of cell biological processes, including the endocytic pathway, ESCRT machinery, autophagy, secretory pathway, intracellular transport, and exocytosis mechanisms. Finally, we speculate about potential relationships between cellular defenses against oligomerizing or aggregating membrane proteins and the envelopment and egress of viruses.

Highlights

The alphaherpesviruses include important human pathogens herpes simplex viruses 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and various veterinary viruses
Given our collective knowledge of the alphaherpesvirus tegument, we find it more useful to think about tegument proteins in terms of their connectivity within the protein interaction network, the requirement for assembly and secondary envelopment, and degree of conservation among herpesvirus subfamilies
Future work is needed to identify which viral membrane and tegument proteins may be present on the cytosolic face of viral secretory vesicles, and determine how these viral proteins interact with host cell biology to modulate virus particle egress, identify additional cell biological factors involved, and demonstrate the function of these viral and cellular factors in virion exocytosis

Summary

Introduction

The alphaherpesviruses include important human pathogens herpes simplex viruses 1 and 2 (HSV-1 and -2), varicella-zoster virus (VZV), and various veterinary viruses. A multitude of viral mechanisms, host cell biological mechanisms, and virus-host interactions drive tegument assembly, secondary envelopment, intracellular trafficking, and exocytosis of progeny virus particles from the infected cell.

Results

Conclusion