Low transduction efficiencies of viral and non-viral vectors still remain a major limitation in suicide gene therapy. The HSV-1 tegument protein VP22 can spread from cells where it is produced to surrounding recipient cells, thus making it a promising tool for compensation of inadequate gene transfer efficiencies. In our previous study, we focused on the optimization of the cytosine deaminase (...

The tegument of herpesvirus virions is a distinctive structure whose assembly and function are not well understood. The herpes simplex virus type 1 VP22 tegument protein encoded by the UL49 gene is conserved among the alphaherpesviruses. Using cell biology and viral genetics, we provide an initial characterization of the pseudorabies virus (PRV) VP22 homologue. We identified three isoforms of V...

Cell-penetrating peptides (CPPs) are non-invasive vectors that can efficiently transport bioactive cargo across the cell membrane. Naturally occurring CPPs, such as the tegument protein VP22 of the Herpes simplex virus type 1, can potentiate protein-drug delivery into living cells. The aim of the present study was to construct anti-VP22 antibodies that can be used to detect VP22-fusion drugs. T...

Although the herpes simplex virus type 1 (HSV-1) tegument is comprised of a large number of viral and cellular proteins, how and where in the cell these proteins are recruited into the virus structure is poorly understood. We have shown previously that the immediate-early gene product ICP0 is packaged by a mechanism dependent on the major tegument protein VP22, while others have shown a require...

The role of phosphorylation in the dissociation of structural components of the herpes simplex virus type 1 (HSV-1) tegument was investigated, using an in vitro assay. Addition of physiological concentrations of ATP and magnesium to wild-type virions in the presence of detergent promoted the release of VP13/14 and VP22. VP1/2 and the UL13 protein kinase were not significantly solubilized. Howev...

VP22, encoded by the UL49 gene of Marek's disease virus (MDV), is indispensable for virus cell-to-cell spreading. We show herein that MDV UL49 can be functionally replaced with avian and human viral orthologs. Replacement of MDV VP22 with that of avian gallid herpesvirus 3 or herpesvirus of turkey, whose residue identity with MDV is close to 60%, resulted in 73 and 131% changes in viral spreadi...

Assembly of the herpesvirus tegument is poorly understood but is believed to involve interactions between outer tegument proteins and the cytoplasmic domains of envelope glycoproteins. Here, we present the detailed characterization of a multicomponent glycoprotein-tegument complex found in herpes simplex virus 1 (HSV-1)-infected cells. We demonstrate that the tegument protein VP22 bridges a com...

The virion host shutoff (vhs) protein encoded by the U(L)41 gene of herpes simplex virus 1 is an endoribonuclease. The enzyme is introduced into the cell during unpackaging of the virion upon entry and selectively degrades mRNA for several hours. The RNase activity ceases after the onset of synthesis of late (gamma) viral proteins. Here we report that vhs protein does not accumulate in cells tr...

We examine biochemical characteristics of the herpes simplex virus (HSV) tegument protein VP22 by gel filtration, glycerol sedimentation, and chemical cross-linking experiments and use time course radiolabeling and immunoprecipitation assays to analyze its synthesis and interaction with other infected-cell proteins. VP22 was expressed as a delayed early protein with optimal synthesis requiring ...

Niemann-Pick disease type C (NPC) is a genetic disorder in which patient cells exhibit lysosomal accumulation of cholesterol and sphingolipids (SLs) caused by defects in either NPC1 or NPC2 proteins. We previously demonstrated that NPC1 human skin fibroblasts overexpressing endosomal Rab proteins (Rab7 or Rab9) showed a correction in the storage disease phenotype. In the current study, we used ...