Nuclear Localization and Shuttling of Herpes Simplex Virus Tegument Protein VP13/14

Abstract

The herpes simplex virus type 1 gene UL47 encodes the tegument proteins referred to collectively as VP13/14, which are believed to be differentially modified forms of the same protein. Here we show that the major product of the UL47 gene during transient expression is VP14, suggesting that some feature of virus infection is required to produce VP13. We have tagged VP13/14 with green fluorescent protein and have demonstrated that the protein is targeted efficiently to the nucleus, where it often localizes in numerous punctate domains. Furthermore, we show that removal of the N-terminal 127 residues of the protein abrogates nuclear accumulation, and we have identified a 14-amino-acid peptide from this region that is sufficient to function as a nuclear targeting signal and transport a heterologous protein to the nucleus. This short peptide contains two runs of four arginine residues, suggesting that the VP13/14 nuclear localization signal may behave in a manner similar to that of the arginine-rich nuclear localization signals of the retrovirus transactivator proteins Tat, Rev, and Rex. In addition, by using heterokaryon assays, we show that VP13/14 is capable of shuttling between the nucleus and cytoplasm of the cell, a property that may be attributed to three leucine-rich stretches in the C-terminal half of the protein that again bear similarity to the nuclear export signals of Rev and Rex. This is the first demonstration of a tegument protein that is specifically targeted to the nucleus, a feature which may be relevant both during virus entry, when VP13/14 enters the cell as a component of the tegument, and at later times, when large amounts of newly synthesized VP13/14 are present within the cell.

Genetic immunisation of cattle against Bovine herpesvirus 1: glycoprotein gD confers higher protection than glycoprotein gC or tegument protein VP8

“…In COS-7 cells transfected with pCIgC and pCIgD, the glycoproteins gC and gD had a membranous localisation similar to that reported in bovine cells [14,37,47]. VP8 had a nuclear localisation that was also consistent with the previously reported localisation of VP8 in BoHV-1 infected cells [53] and the reported localisation of the homolog protein VP13/14 of HSV-1 in transfected mammalian cells [12]. As expected, truncated forms of the glycoproteins gC and gD localised in the secretory pathways and were found in the supernatant of transfected cells.…”

Determination of Interactions between Tegument Proteins of Herpes Simplex Virus Type 1

“…Previous studies of HSV-1 have suggested that both UL46 and UL47 have a role in enhancing UL48-induced immediate-early viral gene expression (19,40,41). Nuclear localization has been demonstrated for UL47 (8,30), supporting a role in regulation of UL48 activity. Using green fluorescent protein fusion proteins, UL46 was only found in the cytoplasm (38), arguing against a role for regulation of UL48 activity in the whole cell.…”

Selective degradation of mRNAs by the HSV host shutoff RNase is regulated by the U L 47 tegument protein

“…RNA and shuttles between the cytoplasm and the nucleus (28). In injunction with ICP27, U L 47 binds and displaces PABC1 from the poly(A) binding protein complex at the cap structure (29).…”