Structural analysis of herpes simplex virus by optical super-resolution imaging

Laine, Romain F.; Albecka, Anna; van de Linde, Sebastian; Rees, Eric J.; Crump, Colin M.; Kaminski, Clemens F.

Electron microscopy (EM) and electron tomography (ET) studies of HSV-1 have revealed that virus particles have a spherical shape 4 , with diameter ranging from 155 to 240 nm, each containing an icosahedral capsid with a diameter of 125 nm 5, 6 , which contains the viral DNA. The structure of the highly ordered capsid complex has been studied extensively and is now well defined. A partially ordered layer of tegument proteins surrounds the nucleocapsid and the viral envelope encloses the nucleocapsid/tegument core. The envelope carries a set of glycoproteins that are essential for virus entry and viral morphogenesis. Among them, glycoprotein D (gD) mediates interactions with cellular receptors and initiates the cascade of events essential for HSV-1 entry into target cells 7 . The tegument is the most structurally complex layer of the virus, and so far, over 20 tegument proteins have been identified for HSV-1 (ref. 8) . In particular, VP1/2 (also known as pUL36) is the largest tegument protein (4330 kDa) and is essential for HSV-1 entry and assembly 9, 10 . Owing to the interaction of its carboxy terminus with the minor capsid protein pUL25, VP1/2 is often referred to as being a part of the inner tegument. With its binding partner pUL37 (refs 11,12) , VP1/2 plays an essential role in capsid transport on microtubules 13 . In contrast to VP1/2 and pUL37, one of the major tegument proteins VP16 is thought to reside closer to the viral envelope and be a part of the outer tegument. VP16 also interacts with VP1/2 (ref. 14) and induces transcription of immediate-early viral genes, thus playing an important role in the viral life cycle 15 . Owing to its multiple interactions with other viral proteins, VP16 has been proposed to serve as a central organizer for the tegument 12 .