Recent loss-of-function studies highlight the importance of the transcription factor GATA4 in the myocardial response to injury in the adult heart. However, the potential effects of gain-in-function of GATA4 overexpression, and transcription factors in general, is hindered by the fact that transcription factors are neither secreted nor taken up by cells. Chimeric proteins incorporating motifs o...

The potency of naked DNA vaccines is limited by their inability to amplify and spread in vivo. VP22, a HSV-1 protein, has demonstrated the remarkable property of intercellular transport and may thus provide a unique approach for enhancing vaccine potency. Therefore, we created a novel fusion of VP22 with a model Ag, human papillomavirus type 16 E7, in a DNA vaccine that generated enhanced sprea...

S et al. (1) report in a previous issue of PNAS that herpes simplex virus 1 (HSV1) particles contain three RNA-binding proteins. They searched for these proteins to probe the mechanism by which mRNAs are incorporated into herpes virus particles (2–4). As yet, it is not clear whether one of more of these RNAbinding proteins deliver mRNAs to virions, but the identity of one of them led Sciortino ...

VP22, a structural protein of herpes simplex virus, exhibits unusual trafficking properties which we proposed might be exploited in gene and protein delivery applications. To pursue the use of the protein itself for cargo delivery into cells, we developed an expression system for the C-terminal half of VP22, residues 159-301 (VP22.C1), and purified the protein in high yields. Addition of short ...

Adenovirus (Ad)-mediated gene transfer is a promising technology for therapy of a wide variety of genetic disorders of the retina. The tropism of Ad vectors limits their utility to cells that express the coxsackie-adenovirus receptor. Upon ocular delivery, Ad vectors primarily infect the retinal pigment epithelium (RPE) and the Müller cells of the retina. However, the most frequent blinding dis...

Immunogold electron microscopy was used to determine whether the tegument proteins VP13/14, VP22, and VP16 of herpes simplex virus type 1 (HSV1) are components of primary enveloped virions. Whereas VP13/14 and VP22 were not detected in virus particles in the perinuclear space and were present in only mature extracellular virions, VP16 was acquired prior to primary envelopment of the virus at th...

Marek's disease virus (MDV) is an alpha-herpesvirus causing Marek's disease in chickens, mostly associated with T-cell lymphoma. VP22 is a tegument protein abundantly expressed in cells during the lytic cycle, which is essential for MDV spread in culture. Our aim was to generate a pathogenic MDV expressing a green fluorescent protein (EGFP) fused to the N-terminus of VP22 to better decipher the...

The ORF9 protein, a VZV-encoded late protein consisting of 302 amino acid (aa) residues, is a member of the highly conserved alphaherpesvirus UL49 gene family but shares limited identity with the UL49 prototype, HSV-1 VP22. As the orthologue of HSV-1 VP22, ORF9 is believed to be a major constituent of the VZV virion tegument. HSV-1 VP22 has been extensively studied; however, the functional prop...

An earlier report has shown that herpes simplex virus 1 virions package RNA. Experiments designed to reveal the identity of the virion proteins capable of binding the RNA and to show whether the mRNA carried in the newly infected cells was expressed showed the following: (i) (32)P-labeled riboprobe generated by in vitro transcription of the U(S)8.5 ORF bound three proteins identified as the pro...

Gene transfer vectors derived from human immunodeficiency virus (HIV-1) efficiently transduce nondividing cells and may provide for the delivery of their gene products to discrete regions of the brain. We investigated whether stable gene transduction can be achieved in cells of the central nervous system (CNS) in vivo by a potent lentivirus vector. The herpes simplex virus type 1 protein VP22 h...