Herpesvirus Assembly and Egress

Abstract

Herpesvirus particles consist of four morphologically distinct structures, the core, capsid, tegument, and envelope. The inner nucleoprotein core comprising the linear double-stranded DNA genome is included in an icosahedral (Tϭ16) capsid shell of 150 hexons and 12 pentons. The capsid is surrounded by a layer of proteinaceous material designated the tegument which, in turn, is enclosed in an envelope of host cell-derived lipids containing virus-encoded (glyco)proteins. Whereas capsid formation in the nuclei of infected cells is understood in some detail, the mechanisms of tegumentation and envelopment and the intracellular compartments involved have long been disputed. This review focuses on recent findings that demonstrate a rather complex process of herpesvirus maturation including primary envelopment of capsids by budding at the inner leaflet of the nuclear membrane and translocation of capsids into the cytoplasm after loss of the primary envelope by fusion with the outer leaflet of the nuclear membrane. Subsequently, final tegumentation occurs in the cytoplasm and tegumented capsids obtain their final envelope by budding into vesicles of the trans-Golgi network. Tegumentation and envelopment are driven by specific protein-protein interactions that appear, at least in cultured cells, to exhibit a remarkable redundancy. NUCLEAR EGRESS: PRIMARY ENVELOPMENTDuring herpesvirus infection, viral transcription, DNA replication, formation of capsids (Fig. 1A and 2A), and packaging of viral DNA occur in the nucleus (32,69,72,84). Subsequently, intranuclear capsids have to leave the nucleus to gain access to the extracellular environment. An early step in nuclear egress of herpesviruses is a budding process at the inner nuclear membrane whereby capsids acquire an envelope derived from the inner leaflet of the nuclear membrane (Fig. 1B and C and 2B and C). Two conserved herpesvirus proteins, the products of the UL31 and UL34 genes (gene designations in accordance with the herpes simplex virus type 1 [HSV-1] genomic sequence are used throughout to avoid confusion due to differences in protein and gene nomenclature among the viruses covered in this review), have recently been demonstrated to be involved in this process. The UL34 gene encodes a type II C-terminally anchored membrane protein (43,63) that is located in pseudorabies virus (PrV)-infected cells in both leaflets of the nuclear membrane (43). The UL31 gene codes for a nuclear phosphoprotein (11) that is also present in the nuclear membrane of infected cells (30,68). The UL31 protein requires UL34 for nuclear membrane targeting (30, 68), whereas the UL34 gene product appears to possess an intrinsic property for targeting to the nuclear membrane (43). However, nuclear membrane localization of the UL34 protein is augmented in the presence of the UL31 gene product (30,68). A physical interaction between the two proteins has recently been demonstrated for the HSV-1 and PrV homologs by using glutathione S-transferase pulldown or yeast two-hybrid analysis (30, 68). Thes...

Copatching and Lipid Raft Association of Different Viral Glycoproteins Expressed on the Surfaces of Pseudorabies Virus-Infected Cells

“…Over the past few years, there have been increasing indications that a very complex network of protein-protein interactions exists between alphaherpesvirus tegument and membrane proteins (31). This complex network is not yet fully understood and is thought to contain many redundant interactions, which makes it, at this time, impossible to carefully assess the contributions of these protein-protein interactions in the copatching behaviors of PRV gB, gC, gD, and gE that we observe here.…”

Bovine herpesvirus 1 infection and infectious bovine rhinotracheitis

“…The current view of egress and maturation of alphaherpesviruses proposes a three step model [63,[124][125][126][127]. In this model, the primary envelope is acquired by the budding of DNA-containing capsids through the inner nuclear membrane.…”

Transport and egress of herpes simplex virus in neurons

“…The enveloped particles are then deenveloped at the outer nuclear membrane. This is followed by the addition of inner tegument onto the capsid before acquisition of outer tegument and secondary envelopment, at the trans-Golgi [8,84]. Fully assembled virions are finally released by exocytosis.…”