Inhibition of Transient Gene Expression with Plasmids Encoding Herpes Simplex Virus Type 1 UL55 and Alpha Genes

Block, Timothy M.; Jordan, Robert; Farkas, Daniel H.; Hughes, Robert G.

doi:10.1099/0022-1317-72-1-131

Cited by 8 publications

(9 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Herpes simplex virus 1 (HSV-1) UL55, the UL4P homolog, was demonstrated to inhibit transient gene expression when co-transfected into cells along with plasmids expressing the immediate early gene α27 as well as alpha genes α0 and α4 (Block et al, 1991). Additionally, Yamada and coworkers (1998) characterized the UL55 protein of HSV-2 as a potential accessory protein in virion assembly and maturation and found it to co-localize with capsid protein ICP35 at the periphery of infected cell nuclei.…”

Section: Resultsmentioning

confidence: 99%

The UL4 protein of equine herpesvirus 1 is not essential for replication or pathogenesis and inhibits gene expression controlled by viral and heterologous promoters

et al. 2011

View full text Add to dashboard Cite

Defective interfering particles (DIP) of equine herpesvirus 1 (EHV-1) inhibit standard virus replication and mediate persistent infection. The DIP genome is comprised of only three genes: UL3, UL4, and a hybrid gene composed of portions of the IR4 (EICP22) and UL5 (EICP27) genes. The hybrid gene is important for DIP interference, but the function(s) of the UL3 and UL4 genes are unknown. Here, we show that UL4 is an early gene activated solely by the immediate early protein. The UL4 protein (UL4P) was detected at 4 hours post-infection, was localized throughout the nucleus and cytoplasm, and was not present in purified virions. EHV-1 lacking UL4P expression was infectious and displayed cell tropism and pathogenic properties in the mouse model similar to those of parental and revertant viruses. Reporter assays demonstrated that the UL4P has a broad inhibitory function, suggesting a potential role in establishing and/or maintaining DIP-mediated persistent infection.

show abstract

Section: Resultsmentioning

confidence: 99%

The UL4 protein of equine herpesvirus 1 is not essential for replication or pathogenesis and inhibits gene expression controlled by viral and heterologous promoters

et al. 2011

View full text Add to dashboard Cite

show abstract

“…VZV contains a UL3 homologue (ORF2), but the function of its corresponding protein is not known [31][32][33]. Studies with HSV-1 UL55, a UL4 homolog, indicated that it may have a negative regulatory function during lytic infection [34]. While it is unknown as to whether EHV-1 UL4 shares this function, it is tempting to hypothesize that during persistent infection UL4 could down-regulate standard virus gene expression via a gene dosage effect.…”

Section: Discussionmentioning

confidence: 99%

Genetic Complexity of EHV-1 Defective Interfering Particles and Identification of Novel IR4/UL5 Hybrid Proteins Produced During Persistent Infection

Ebner

O’Callaghan

2006

Virus Genes

View full text Add to dashboard Cite

This study examined the genetic complexity of three equine herpesvirus 1 (EHV-1) defective interfering particles (DIP) and found the DIP genomes to range from 5.9 kbp to 7.3 kbp in total size. Each DIP contains an identical 5' end ( approximately 1.9 kb) that harbors UL3 and UL4 genes that are 100% identical to those of the infectious virus. DIP2 and DIP3 contain a previously described unique IR4/UL5 (EICP22/EICP27) hybrid gene (Hyb1.0). The DIP1 genome, however, appears to be generated from a different recombination event which results in the formation of a new distinct hybrid ORF. The new ORF (Hyb2.0) is comprised of 684 bp from the 5' end of IR4 fused to 45 bp from the 3' terminus of UL5. In contrast to Hyb1.0, the UL5 sequences present in Hyb2.0 are not in-frame. Thus, the Hyb2.0 protein is comprised of 228 residues from IR4 linked to a sequence of 15 amino acids that result from a frameshifted reading of UL5 sequences. Western blot analysis confirmed that the Hyb2.0 ORF is expressed during persistent infection to produce a family of proteins that migrate at 36-42 kDa. Fluorescence microscopy revealed that both Hyb proteins display diffuse cytoplasmic localization patterns dissimilar to the nuclear localization patterns of both IR4 and UL5. Neither Hyb protein, however, disrupts the nuclear entry of the EHV-1 immediate-early, IR4, or UL5 proteins or cellular TATA box binding protein (TBP) previously shown to interact with both IR4 or UL5 in productive infection. DIP genomic segments ( approximately 3.5-5.0 kbp) downstream of the 100% conserved origin of replication are highly variable among the three DIP genomes and contain large areas of repetitive sequences. The possibility that the non-coding sequences play a role in viral interference and/or persistent infection remains to be determined.

show abstract

“…Roles for UL55 and UL56 have been suggested. For example, Block et al (1991) indicated that either gene product may act to control Vmw63 synthesis. However, it has already been shown that UL55 and UL56 are dispensable in tissue culture (Brown et al, 1984;Harland & Brown, 1988;MacLean & Brown, 1987a, b).…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Herpes Simplex Virus type 1 Deletion Variant (1703) Which Under-produces Vmw63 During Immediate Early Conditions of Infection

Mc¹,

McLauchlan²,

Marsden³

et al. 1994

Journal of General Virology

View full text Add to dashboard Cite

The herpes simplex virus type 1 deletion variant 1703 apparently fails to synthesize the essential IE2 gene product Vmw63 despite the deletion leaving the gene intact. Sequence analysis revealed that the deletion removes a region to the right of IE2 comprising the 3' end of IE1, UL56 and the 3' part of UL55, stopping 555 bp downstream of the IE2 polyadenylation signal. Further DNA sequencing has shown that there is no secondary mutation in the IE2 gene. Western blot analysis demonstrated that Vmw63 is made at reduced levels compared to that produced by the wild-type virus during immediate early conditions of infection. S1 nuclease protection mapping has revealed that this reduction is also apparent at the level of mRNA synthesis. A direct link between the deletion and the change in mRNA synthesis was provided by the insertion of a deletion-spanning fragment from 1703 into a 17 + genome, which resulted in the recombinant having a 1703-like phenotype. Evidence that down-regulation of IE2 mRNA during immediate early conditions of infection could be due to antisense RNA initiating from the IE1 promoter was obtained by the insertion of a novel transcriptional termination signal between IE1 and IE2 in the variant and the subsequent detection of wild-type levels of IE2 mRNA and protein. IntroductionHerpes simplex virus type 1 (HSV-1) has five immediate early genes (IE1, 2, 3, 4 and 5) encoding the polypeptides Vmwll0, 63, 175, 68 and 12 respectively. Immediate early genes are unique in that they are transcribed in the absence of prior viral protein synthesis and their products are required for the expression of early and late viral polypeptides. The immediate early genes and their encoded proteins have been the subject of close scrutiny and much information has been gained concerning their regulatory activities and functional domains. The isolation and characterization of temperature-sensitive (ts) IE2 mutants demonstrated that Vrnw63 played an essential role in virus replication (Sacks et al., 1985) and the characterization of null mutants in this gene demonstrated the role of Vmw63 in the modulation of early and late gene expression at the transcriptional level (McCarthy et al., 1989). Further analysis demonstrated that Vmw63 performs its regulatory activities over time and mediates these activities indirectly via interactions with, and modification of Vmw175 and possibly other viral and cellular proteins (Rice et al., 1989; '~Present address: Department of Microbiology, The University, Glasgow G12 8QQ, U.K. & Schaffer, 1990). Recent evidence indicates that Vmw63 may be involved at post-transcriptional levels to affect viral mRNA Y processing (Sandri-Goldin & Mendoza, 1992;McLauchlan et al., 1992).In 1987 we reported the isolation of an HSV-1 strain 17 + variant (1703) with a 7'5 kb deletion encompassing part of the long internal repeat region (IRL) and the adjacent unique sequences, such that most of one copy of the IE1 gene, part of UL55 and all of UL56 were deleted (MacLean & Brown, 1987a). The deletion terminate...

show abstract

Inhibition of Transient Gene Expression with Plasmids Encoding Herpes Simplex Virus Type 1 UL55 and Alpha Genes

Cited by 8 publications

References 32 publications

The UL4 protein of equine herpesvirus 1 is not essential for replication or pathogenesis and inhibits gene expression controlled by viral and heterologous promoters

The UL4 protein of equine herpesvirus 1 is not essential for replication or pathogenesis and inhibits gene expression controlled by viral and heterologous promoters

Genetic Complexity of EHV-1 Defective Interfering Particles and Identification of Novel IR4/UL5 Hybrid Proteins Produced During Persistent Infection

Characterization of a Herpes Simplex Virus type 1 Deletion Variant (1703) Which Under-produces Vmw63 During Immediate Early Conditions of Infection

Contact Info

Product

Resources

About