Navigating the Cytoplasm: Delivery of the Alphaherpesvirus Genome to the Nucleus

Abstract

Herpesviruses virions are large and complex structures that deliver their genetic content to nuclei upon entering cells. This property is not unusual as many other viruses including the adenoviruses, orthomyxoviruses, papillomaviruses, polyomaviruses, and retroviruses, do likewise. However, the means by which viruses in the alphaherpesvirinae subfamily accomplish this fundamental stage of the infectious cycle is tied to their defining ability to efficiently invade the nervous system. Fusion of the viral envelope with a cell membrane results in the deposition of the capsid, along with an assortment of tegument proteins, into the cytosol. Establishment of infection requires that the capsid traverse the cytosol, dock at a nuclear pore, and inject its genome into the nucleoplasm. Accumulating evidence indicates that the capsid is not the effector of this delivery process, but is instead shepherded by tegument proteins that remain capsid bound. At the same time, tegument proteins that are released from the capsid upon entry act to increase the susceptibility of the cell to the ensuing infection. Mucosal epithelial cells and neurons are both susceptible to alphaherpesvirus infection and, together, provide the niche to caister.com/cimb 171 Curr. Issues Mol. Biol. Vol. 41Navigating the Cytoplasm Smith which these viruses have adapted. Although much has been revealed about the functions of de novo expressed tegument proteins during the late stages of assembly and egress, this review will specifically address the roles of tegument proteins brought into the cell with the incoming virion, and our current understanding of alphaherpesvirus genome delivery to nuclei.

Oncolytic herpes simplex virus armed with a bacterial GBP1 degrader improves antitumor activity

“…GBP1 remodels the host actin cytoskeleton, whereas HSV-1 hijacks the host cytoskeleton for capsid trafficking. 27 , 28 , 29 Therefore, we hypothesize that GBP1 disturbs actin cytoskeleton to hinder HSV-1 capsid trafficking. To test this hypothesis, we first treated HSV-1-infected cells with a widely used actin cytoskeleton polymerization inhibitor, cytochalasin D (CytoD), and found that CytoD treatment effectively disrupted cytoskeletal organization ( Figure 5 A) and impeded the nuclear translocation of the HSV-1 genome as expected ( Figures 5 B and 5C).…”

Intranuclear HSV-1 DNA ejection induces major mechanical transformations suggesting mechanoprotection of nucleus integrity

“…As mentioned above, during HSV-1 reactivation from latency in TG neurons at high MOI ( 17 – 19 ), tens of HSV-1 virus capsids simultaneously adsorb to NPCs on a single cell nucleus and eject viral genomes ( 10 , 11 ). [This process is repeated as empty capsids detach and new DNA-loaded capsids are docked at the NPCs in vivo ( 35 ).] A single round of HSV-1 DNA ejections leads to internalization of millions of base pairs of viral DNAs in the nucleus; HSV-1 DNA quickly decondenses once in the nucleus, occupying three times more volume than in the capsid ( 36 ).…”

Tegument proteins of Epstein-Barr virus: Diverse functions, complex networks, and oncogenesis

“…For comparison, a PPI network centering on HSV tegument proteins was also generated ( Fig. 2 ) [ 2 , 7 , [24] , [25] , [26] , [27] ]. Most PPIs have been detected in lysates (by immunoprecipitation) or cells (yeast two-hybrid or complementation assay of split marker), but not in the tegument.…”

“…The tegument of herpesviruses is mainly composed of viral proteins, with some cellular proteins. Tegument proteins do not comprise a solid structure like the nucleocapsid and, thus, a portion of the tegument structure can be released into the cytoplasm when the viral envelope fuses with the plasma membrane or endosomal membrane [ 2 ]. Some types of tegument proteins form interfaces with the exterior of the nucleocapsid (the inner tegument), and some others with membrane proteins on the interior surface of the envelope (outer tegument).…”