Have NEC Coat, Will Travel

Abstract

Herpesviruses are unusual among enveloped viruses because they bud twice yet acquire a single envelope. Furthermore, unlike other DNA viruses that replicate in the nucleus, herpesviruses do not exit it by passing through the nuclear pores or by rupturing the nuclear envelope. Instead, herpesviruses have a complex mechanism of nuclear escape whereby nascent capsids bud at the inner nuclear membrane to form perinuclear virions that subsequently fuse with the outer nuclear membrane, releasing capsids into the cytosol. This makes them some of the very few known viruses that bud into the nuclear envelope. The envelope acquired during nuclear budding does not end up in the mature viral particle but instead allows the capsid to translocate from the nucleus into the cytosol. The viral nuclear egress complex (NEC) is a critical player in the nuclear egress, yet its function and mechanism have remained enigmatic. Recent studies have demonstrated that the NEC buds membranes without the help of other proteins by forming a honeycomb coat, which established the NEC as the first virally encoded budding machine that operates at the nuclear, as opposed to cytoplasmic, membrane. This review discusses our current understanding of the NEC budding mechanism, with the emphasis on studies that illuminated the structure of the NEC coat and its role in capsid budding during herpesvirus nuclear escape.

Patterns of Autologous and Nonautologous Interactions between Core Nuclear Egress Complex (NEC) Proteins of α-, β- and γ-Herpesviruses

“…Functional details of NEC assembly and the regulatory role of NECs in nuclear egress appear closely related and almost congruent between herpesviruses in several aspects, such as recruiting effector proteins responsible for nuclear lamina rearrangement ( Figure 1) [2,27]. Similarly, many structural properties of NEC proteins were also found conserved and qualitatively mostly consistent [28,29]. It appeared all the more unexpected that levels of sequence conservation, in terms of amino acid identity, are quite limited or low, even between members within herpesviral subfamilies (Table 1).…”

Endoplasmic reticulum-to-Golgi transitions upon herpes virus infection

“…Budding requires proteins that are able to induce positive and negative curvatures. Budding at the INM is driven by UL31/UL34 ( Bigalke & Heldwein, 2016; Bigalke & Heldwein, 2017; Bigalke et al , 2014; Hagen et al , 2015). UL31 and UL34 are also present at the ONM even in cells infected with Us3 deletion mutants ( Reynolds et al , 2002) those envelopes are unable to fuse with the ONM ( Reynolds et al , 2002; Wisner et al , 2009).…”

HSV-1 Cytoplasmic Envelopment and Egress

“…Following reactivation from latency, the HSV-1 genome is replicated and packaged into preassembled viral procapsids [ 1 , 11 , 14 ]. DNA-containing nucleocapsids then bud into the inner nuclear membrane and pinch off as primary enveloped virions into the perinuclear space, a process catalyzed by the UL31p/UL34p nuclear export complex [ 15 , 16 ]. The fusion of this primary envelope with the outer nuclear membrane delivers the capsid into the cytoplasm [ 15 , 16 , 17 , 18 , 19 ].…”

“…DNA-containing nucleocapsids then bud into the inner nuclear membrane and pinch off as primary enveloped virions into the perinuclear space, a process catalyzed by the UL31p/UL34p nuclear export complex [ 15 , 16 ]. The fusion of this primary envelope with the outer nuclear membrane delivers the capsid into the cytoplasm [ 15 , 16 , 17 , 18 , 19 ]. The shell of the mature HSV-1 icosahedral capsid is composed of the major capsid protein UL19p (VP5) which assembles into capsomeres; pentamers (pentons) at the vertices and hexamers (hexons) on the icosahedral faces ( Figure 1 ) [ 11 , 20 , 21 ].…”