Disease relevance of US11

• Herpes simplex virus-1 US11 is a RNA-binding protein with a novel RNA-binding domain [1].
• Densitometric analysis of purified virions showed that the levels of VP11/12 and VP13/14 in the virion tegument were near the molar ratios of alpha TIF [2].
• Thus, although required for efficient replication, the myristylated HSV-1 virion protein, in contrast to those of many other viruses, is not essential for virus growth in tissue culture [3].
• L-particles are noninfectious virion-related particles that lack the nucleocapsid but do contain tegument and envelope [4].
• An oligonucleotide consisting of 19 nucleotides spanning the TATA box of the HSV-1 true late US11 gene drove barely detectable levels of expression; by contrast, the corresponding regions of the Adenovirus type 2 major late promoter and the HSV-1 true late glycoprotein C promoter were much more active [5].

High impact information on US11

• The infectious virion is an enveloped capsid containing the viral polymerase and double-stranded DNA genome [6].
• We propose that when the intrinsic capacity of neurons to inhibit HSV-1 reactivation from latency is compromised, production of HSV-1 immediate early and early proteins might activate CD8(+) T cells aborting virion production [7].
• The herpes simplex virus 1 ORF U(L)41 encodes a protein (virion host shutoff or vhs) associated with selective degradation of mRNA early in infection [8].
• We conclude that (i) three virion proteins are capable of binding RNA; (ii) the packaged RNA can be expressed in newly infected cells; and (iii) the U(L)47 protein was earlier reported to shuttle from nucleus to the cytoplasm and may transport RNA [9].
• Several laboratories have shown that transfected plasmid DNAs containing either of the two known origins of herpes simplex virus (HSV) DNA replication, oriS or oriL, are replicated in HSV-1-infected cells or in cells cotransfected with virion DNA [10].

Chemical compound and disease context of US11

• By microinjecting purified glutathione S-transferase linked to all or parts of herpes simplex virus type 1 US11 protein into either the nucleus or the cytoplasm, we have demonstrated that this nucleolar protein exhibits a new type of localization signal controlling both retention in nucleoli and export to the cytoplasm [11].
• A herpes simplex virus 1 US11-expressing cell line is resistant to herpes simplex virus infection at a step in viral entry mediated by glycoprotein D [12].
• To test this possibility, we engineered a peptide with affinity for immobilized cobalt in frame in the heparan sulfate binding domain of HSV-1 glycoprotein B, which is known to be exposed on the surface of the virion particle and recombined into the viral genome [13].
• These results show for the first time that sialic acids on HSV-1 virions play an important role in infection and suggest that targeting virion sialic acids may be a valid antiviral drug development strategy [14].
• To provide a means of investigating the activity of VP16 on IE promoters not located in the HSV-1 genome, cell lines containing the neomycin phosphotransferase gene controlled by the HSV-1 IE ICPO promoter were constructed [15].

Biological context of US11

• Binding of herpes simplex virus-1 US11 to specific RNA sequences [1].
• The US11 RNA-binding domain and < or =46 bases of selected RNA containing the consensus sequence were each sufficient for binding [1].
• The phosphorylation of virion-associated VP13/14, VP16, and VP22 was demonstrated in cells infected in the presence of cycloheximide [16].
• The myristylated virion proteins of herpes simplex virus type 1: investigation of their role in the virus life cycle [3].
• A feature of the cascade regulation of herpes simplex virus 1 gene expression in productive infection is that the first genes to be expressed, the alpha genes, are transactivated by a structural component of the virion designated as the alpha transinducing factor (alpha TIF) [17].

Anatomical context of US11

• We propose a model for infectious entry of HSV-1 by a series of interactions between the virion envelope and the cell plasma membrane that trigger virion disassembly, membrane fusion, and capsid penetration [18].
• The site of the defect in retrograde spread remains to be determined; however, infection of rat superior cervical ganglia neurons in vitro indicates that gE is required to target virion components to the axon initial segment [19].
• A baby hamster kidney [BHK(tk-)] cell line (US11cl19) which stably expresses the US11 and alpha 4 genes of herpes simplex virus 1 strain F [HSV-1(F)] was found to be resistant to infection with HSV-1 [12].
• US11 localizes to the nucleolus in infected cells, can associate with ribosomes, and has been shown to bind RNA [20].
• Input virion-associated VP13/14 and VP16 localized to the nucleus early in infection, while VP1/2 localized to the nuclear envelope of the cell and VP22 could not be detected using monoclonal antibody P43 [21].

Associations of US11 with chemical compounds

• US11 binding protected the consensus motif from hydroxyl radical cleavage [1].
• Oncolysis by a replicating HSV-1 mutant combined with therapeutic transgene delivery represents a new paradigm; HSV1yCD-infected cells are destroyed by viral replication, and uninfected cells are subjected to bystander killing from both progeny virion and extracellular diffusion of 5-FU [22].
• We confirmed that gB, gC, and gD could be cross-linked to each other on the virion surface but found that the absence of one glycoprotein did not alter the outcome of cross-linking reactions between the remaining molecules [23].
• Entry was not inhibited by bafilomycin A1 or ammonium chloride, showing that passage of the virion through a low-pH environment was not required for infection [24].
• In the presence of Roscovitine, the level of virion-induced activation of a transfected reporter gene (the gene encoding chloramphenicol acetyltransferase) linked to the promoter-regulatory region of the ICP0 gene was reduced 40-fold relative to that of untreated samples [25].

Regulatory relationships of US11

• These experiments revealed that this interaction has biological activity; at early times of infection, US11 down-regulates UL13 protein kinase mRNA and protein [20].

Other interactions of US11

• To elucidate the role of US11 in the virus life cycle, we infected cells with wild-type virus, a cosmid-reconstructed US11 HSV-1 null mutant, and a cosmid-reconstructed wild-type virus and analyzed expression of UL12, -13, and -14 during a time course of infection [20].
• US1.5 protein must be posttranslationally modified by the UL13 protein kinase to enable expression of a subset of late genes exemplified by UL38 and US11 [26].
• Intercellular trafficking and cytotoxicity of recombinant HSV-1 thymidine kinase fused with HSV-2 US11 RXP repeat peptide [27].
• Gene UL11 of herpes simplex virus type 1 encodes a virion protein which is myristylated [28].

Analytical, diagnostic and therapeutic context of US11

• Western blotting suggested that virion-associated VP13/14, VP16 and VP22 were stable in infected cells whereas VP1/2 appeared to be processed or modified [21].
• (i) Only a fraction of viral ORF transcripts were represented in virion RNA, and only nine RNAs (U(L)10, U(L)34/U(L)35, U(L)36, U(L)42, U(L)48, U(L)51, U(S)1/U(S)1.5, U(S)8.5, and U(S)10/U(S)11) were positive in all RT PCR assays [29].
• Kinetic and morphological features of intranuclear and extranuclear virion trafficking have similarly been examined by indirect immunofluorescence microscopy and electron microscopy [30].
• We have employed an oligonucleotide microarray to examine the effect of VP16 mutations on the overall pattern of viral gene expression following infection of HeLa cells [31].
• Site-directed mutagenesis of the virion host shutoff gene (UL41) of herpes simplex virus (HSV): analysis of functional differences between HSV type 1 (HSV-1) and HSV-2 alleles [32].

References