Disease relevance of US11

• US11 is a small basic protein composed of 161 amino acid residues, and is among the most abundant viral proteins in cells infected with herpes simplex viruses HSV1 and HSV2 [1].
• To improve the therapeutic efficacy of herpes simplex virus type 1 (HSV-1) thymidine kinase (tk)/ganciclovir (GCV) therapy, we have made recombinant tk chimeras fused with the arginine-rich (RXP) repeat of herpes simplex virus type 2 (HSV-2) US11 and examined their activity of intercellular trafficking and cytotoxicity [2].
• No virion-associated inhibition of cellular protein synthesis or vhs-induced cellular mRNA degradation was detected in cells infected with any of three EHV-1 strains (Ab4, KyA, and KyD) at multiplicities of infection at which HSV-1 strain F exhibited maximal vhs activity [3].
• Following HSV-1 superinfection of transfected HeLa cells, the US11 promoter in ORI+ plasmids was expressed with similar kinetics to the viral US11 promoter [4].
• US11 protein resembles the tat protein of human immunodeficiency virus with respect to size, charge, nucleolar accumulation, and possibly effect on accumulation of its target RNA but does not share with it discernible sequence homology [5].

High impact information on US11

• The hbx protein was detected in hepatitis B virions, and tryptic phosphopeptide maps of the hbx protein phosphorylated in the virion and of the in vitro phosphorylated bacterially expressed hbx protein were similar [6].
• Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation [7].
• Structure and role of the herpes simplex virus DNA termini in inversion, circularization and generation of virion DNA [8].
• Although it is known that the virion uses a basic fibroblast growth factor (FGF) receptor to penetrate vascular cells, it is not known how the viral particle recognizes and binds to this cell surface protein [9].
• Mutation of Cys211 in the CXXX box of the large antigen abolished both prenylation and particle formation, suggesting that this site is important for virion morphogenesis [10].

Chemical compound and disease context of US11

• Highly specific and sensitive probes were used to monitor US11 RNA and protein synthesis during HSV-1 infection of tissue culture cells in the presence and absence of phosphonoacetic acid, an inhibitor of viral DNA replication [11].
• Microsequencing of a cyanogen bromide peptide obtained from a basic phosphoprotein co-sedimenting with purified ribosomes extracted from herpes simplex virus type 1-infected human epidermoid carcinoma 2 cells identified this protein as a product of the true late US11 gene [12].
• Membrane proteins specified by herpes simplex viruses. III. Role of glycoprotein VP7(B2) in virion infectivity [13].
• Photodynamic treatment of herpes simplex virus type 1-infected hamster embryo fibroblasts (LSH strain) with a low concentration of proflavine (0.08 mug/10(5) cells per ml), a 3-9-diamine acridine dye, inhibited production not only of infectious progeny but also of virion particles [14].
• The initial step in herpes simplex virus (HSV) entry is binding of virion glycoprotein (g)C and/or gB to cell surface heparan sulfate [15].

Biological context of US11

• We have investigated the basis of the different shutoff phenotypes of a strong shutoff strain (HSV-2 strain G), a weak shutoff virus (HSV-1 strain 17 syn+) and HG52 by comparative DNA sequence analysis of gene UL41, which encodes the virion-associated host shutoff factor [16].
• To enhance these properties while employing ample safeguards, two conditionally replicating HSV-1 vectors, termed G47Delta and R47Delta, have been constructed by deleting the alpha47 gene and the promoter region of US11 from gamma34.5-deficient HSV-1 vectors, G207 and R3616, respectively [17].
• Sequences containing the IE-5 promoter (a 3' co-terminal gene whose transcription starts 5' of US11) also played a positive role in achieving normal US11 gene expression [4].
• In a transient assay system, regulation of a plasmid-borne US11 promoter mimics its viral counterpart, and has a similar dependence on DNA replication for abundant expression [18].
• Expression of US11 RNA was detectable from non-replicating ORI- plasmids, although transcript accumulation was reduced by greater than 90% [4].

Anatomical context of US11

• We demonstrate that the US11 protein has intercellular trafficking activity and accumulates in the nucleolus when singly expressed in cultured cells, and that the RXP repeats are responsible for this activity [19].
• Finally, crossing the nuclear pore complex from the cytoplasm to the nucleus is an energy-dependent process for US11 protein, while getting to nucleoli through the nucleoplasm is energy independent [20].
• US11 protein expressed in an uninfected cell line stably transfected with the US11 gene associates with ribosomal 60S subunits and localizes to nucleoli, suggesting that US11 protein requires no other viral functions for these associations [21].
• The great majority of cytoplasmic US11 protein was found in association with the 60S subunit of infected cell ribosomes [21].
• The US11 function is the only viral function required, since translation in rabbit reticulocyte lysate of an in vitro-synthesized US11 mRNA resulted in the appearance of the RNA-binding activity [22].

Associations of US11 with chemical compounds

• This US11 protein, which has phosphates on multiple serine residues, is brought into the cell by the virion and found to be present within ribosome fractions early after infection [12].
• Antisera prepared against the three sodium dodecyl sulfate-dissociated structural polypeptides (VP-1, VP-2, and VP-3) of AAV-3 and against the whole AAV-3 virion were used as probes to search for AAV-3 FA-stainable antigens synthesized by these cells [23].
• Extensive mutagenesis at position 442 of the truncated VP16 activation domain (delta 456), normally occupied by a phenylalanine residue, demonstrated the importance of an aromatic amino acid at that position [24].
• On the basis of an alignment of the VP16 sequence surrounding Phe-442 and the sequences of other transcriptional activation domains, we subjected leucine residues at positions 439 and 444 of VP16 to mutagenesis [24].
• The partially glycosylated product is then conjugated further in a slow, discontinuous process to form the mature glycoprotein of the virion and plasma membrane [25].

Regulatory relationships of US11

• The UL14 gene product of herpes simplex virus is a 32kDa protein expressed late in infection and is a minor component of the virion tegument [26].
• Identification and characterization of the virion-induced host shutoff product of herpes simplex virus gene UL41 [27].

Other interactions of US11

• The UL46 gene encodes virion tegument phosphoproteins, the properties and functions of which are poorly understood [28].
• The virion-associated function is encoded by the viral gene UL41 [29].
• Assembly of enveloped tegument structures (L particles) can occur independently of virion maturation in herpes simplex virus type 1-infected cells [30].

Analytical, diagnostic and therapeutic context of US11

• Liquid chromatography/tandem mass spectrometry of synthesis products associated with the viral protein US11 [1].
• Serial passage in human cells of a mutant lacking the gamma134.5 gene yields second-site, compensatory mutants lacking various domains of the alpha47 gene situated next to the US11 gene (I. Mohr and Y. Gluzman, EMBO J. 15:4759-4766, 1996) [31].
• Flow cytometry was used to analyze the phagocytosis of fluorescence-labeled viruses and demonstrated that although a virion is able to associate with PMN in the presence of complement alone, the granulocyte is not triggered to mount a metabolic burst [32].
• These results, demonstrating intracellular transport of large functional proteins, indicate that VP22 delivery may have applications in gene therapy [33].
• Structural features of the transcriptional activation domain of the herpes simplex virion protein VP16 were examined by oligonucleotide-directed mutagenesis [24].

References