Disease relevance of UL49

• Characterization of a UL49-null mutant: VP22 of herpes simplex virus type 1 facilitates viral spread in cultured cells and the mouse cornea [1].
• Using the polymerase chain reaction we have cloned the UL49 open reading frame into a mammalian expression vector under the control of the human cytomegalovirus immediate early gene promoter [2].
• The varicella-zoster virus (VZV) ORF9 protein is a member of the herpesvirus UL49 gene family but shares limited identity and similarity with the UL49 prototype, herpes simplex virus type 1 VP22 [3].
• The HSV-1 tegument is composed of at least 20 different viral proteins of various stoichiometries [1].
• Herpes simplex virus type 1 (HSV-1) virions, like those of all herpesviruses, contain a proteinaceous layer termed the tegument that lies between the nucleocapsid and viral envelope [1].

High impact information on UL49

• Of the three tegument proteins that package mRNA in herpes simplex virions, one (VP22) transports the mRNA to uninfected cells for expression prior to viral infection [4].
• Nuclear transport of the viral tegument protein VP16, transport of viral capsids to the nuclear pore, and downstream events (including expression of immediate-early genes and viral plaque formation) were substantially reduced in cells transfected with dominant-negative mutants of FAK or small interfering RNA designed to inhibit FAK expression [5].
• We have previously shown (G. E. Lee, G. A. Church, and D. W. Wilson, J. Virol. 77:2038-2045, 2003) that the virion host shutoff (Vhs) tegument protein is largely insoluble in HSV-infected cells and is also stably associated with membranes [6].
• Identification of a 709-Amino-Acid Internal Nonessential Region within the Essential Conserved Tegument Protein (p)UL36 of Pseudorabies Virus [7].
• The remaining interactions consisted of self-associations that were observed for US11, UL37, and UL49 [8].

Chemical compound and disease context of UL49

• Current evidence suggests that viral glycoprotein tails play a role in the recruitment of tegument-coated capsids to the site of final envelopment; vesicles derived from the trans-Golgi network [9].
• The protein kinase associated with purified herpes simplex virus 1 and 2 virions partitioned with the capsid-tegument structures and was not solubilized by non-ionic detergents and low, non-inhibitory concentrations of urea [10].

Biological context of UL49

• Indirect evidence exists to suggest that it is encoded by gene UL49, present in the BamHI F fragment of the genome [2].
• Post-translational modification of the tegument proteins (VP13 and VP14) of herpes simplex virus type 1 by glycosylation and phosphorylation [11].
• Antigenic and protein sequence homology between VP13/14, a herpes simplex virus type 1 tegument protein, and gp10, a glycoprotein of equine herpesvirus 1 and 4 [12].
• The equine herpesvirus 1 (EHV-1) homolog of the herpes simplex virus type 1 (HSV-1) tegument phosphoprotein, alpha TIF (Vmw65; VP16), was identified previously as the product of open reading frame 12 (ORF12) and shown to transactivate immediate early (IE) gene promoters [13].
• Phosphorylation of structural components promotes dissociation of the herpes simplex virus type 1 tegument [14].

Anatomical context of UL49

• The MDV UL49 gene, which encodes the tegument viral protein 22 (VP22), has been expressed as a green fluorescent protein (GFP) fusion protein in chicken embryonic fibroblasts to examine its subcellular localization [15].
• After contact of infectious virus with the cell plasma membrane, discernible changes of the envelope and tegument could be seen by electron microscopy [16].
• After intranuclear assembly, nucleocapsids bud at the inner leaflet of the nuclear membrane, resulting in enveloped particles in the perinuclear space that contain a sharply bordered rim of tegument and a smooth envelope surface [17].
• In this study, we have tested the hypothesis that latent infection of sensory neurons results from the failure of alpha TIF, a tegument protein, to be transported from the nerve endings to the nucleus of the sensory neuron [18].
• Differences in the intracellular localization and fate of herpes simplex virus tegument proteins early in the infection of Vero cells [19].

Associations of UL49 with chemical compounds

• We have identified an interaction between VP22, an abundant tegument protein and the cytoplasmic tail of glycoprotein E (gE) [9].

Analytical, diagnostic and therapeutic context of UL49

• ETIF was localized to the viral tegument in Western blot assays of EHV-1 virions and subvirion fractions using polyclonal antiserum and monoclonal antibodies generated against a glutathione-S-transferase-ETIF fusion protein [13].
• The intercellular trafficking property of the herpes simplex virus type 1 tegument protein VP22 makes it a promising tool for overcoming low transduction efficiencies in gene therapy [20].

References