Herpes Simplex Virus-Mediated Activation of Human Immunodeficiency Virus Is Inhibited by Oligonucleoside Methylphosphonates That Target Immediate-Early mRNAs 1 and 3

Feng, Chu-Pei; Kulka, Michael; Smith, Cynthia C.; Aurelian, Laure

doi:10.1089/oli.1.1996.6.25

Cited by 7 publications

(12 citation statements)

References 56 publications

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“…7C, lane 4). By arbitrarily assigning a value of 1.0 to the degree of expression in normal melanocytes (28), the expression levels in the three melanoma tissues were 47, 96, and 100, respectively. Those in the melanoma cell lines were 92, 150, and 120 for G361, SK-MEL-31, and SK-MEL-2 cells, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…To test this possibility, we took advantage of previous findings from our (28,31,32) and many other (33, 38 -41) laboratories that antisense ODNs specifically inhibit the translation of the targeted genes and thereby their function. G361, SK-MEL-31, and SK-MEL-2 cells were exposed (24 h) to different doses of antisense ODNs complementary to the H11 translation initiation site (aODN-1 and aODN-2) and analyzed for their ability to proliferate, as determined by (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Northern blot hybridization was done exactly as described previously (8,28). The H11 probe was the 1.8-kilobase EcoRI/XhoI cDNA fragment.…”

Section: Construction Of Eukaryotic Expression Vectors For H11 and Thmentioning

confidence: 99%

“…Effect of Antisense Oligonucleotides-Cells (5 ϫ 10 3 ) were incubated in triplicate in 96-well plates in 0.1 ml of culture medium supplemented with 10% heat-inactivated FCS for 30 min at 65°C to destroy nuclease activity and were cultured (24 h) in the presence or absence of antisense, sense, or randomly scrambled phosphorothioate oligonucleotides (ODNs), as described (28,(31)(32)(33). The ODN sequences were first tested against sequences in the GenBank TM data base.…”

Section: Construction Of Eukaryotic Expression Vectors For H11 and Thmentioning

confidence: 99%

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A Novel Human Gene Similar to the Protein Kinase (PK) Coding Domain of the Large Subunit of Herpes Simplex Virus Type 2 Ribonucleotide Reductase (ICP10) Codes for a Serine-Threonine PK and Is Expressed in Melanoma Cells

Smith

Kulka

et al. 2000

Journal of Biological Chemistry

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128

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The large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) is a multifunctional protein that contains a serine-threonine protein kinase (PK) activity (Nelson, J. W., Zhu, J., Smith, C. C., Kulka, M., and Aurelian, L. (1996) J. Biol. Chem. 271, 17021-17027). Phylogenetic analyses indicated that ICP10 PK belongs to a distinct subfamily of growth factor receptor serine-threonine PKs that are characterized by their ability to function with a limited number of conserved catalytic motifs (Hunter, J. C. R., Smith, C. C., and Aurelian, L. (1995) Int. J. Onc. 7, 515-522). Here, we report the isolation and characterization of a novel gene, designated H11, that contains an open reading frame of 588 nucleotides, which encodes a protein similar to ICP10 PK. The H11 protein has Mn 2؉ -dependent serinethreonine-specific PK activity as determined with a GST-H11 fusion protein and by immununocomplex PK/ immunoblotting assays of 293 cells transfected with a H11 eukaryotic expression vector. PK activity is ablated by mutation of Lys 113 within the presumtive catalytic motif II (invariant Lys). 293 cells stably transfected with H11 acquire anchorage-independent growth. Endogenous H11 RNA and the H11 phosphoprotein are expressed in melanoma cell lines and primary melanoma tissues at levels higher than in normal melanocytes and in benign nevi. Melanoma cell proliferation is inhibited by treatment with antisense oligonucleotides that inhibit H11 translation, suggesting that H11 expression is associated with cell growth.Several herpes viruses including herpes simplex virus type 1 (HSV-1) 1 and herpes simplex virus type 2 (HSV-2) express a distinct ribonucleotide reductase activity formed by the association of a large (R1) and a small (R2) subunit. The HSV-2 R1 gene (also known as ICP10) differs from its counterparts in eukaryotic and prokaryotic cells and in other viruses in that it possesses a unique one-third 5Ј-terminal domain (1) that codes for a serine (Ser)-threonine (Thr) protein kinase (PK) (2-8) and causes neoplastic transformation of immortalized cells (9 -11). Unlike other known PKs that have at least 12 conserved catalytic motifs (12, 13), ICP10 PK functions with only eight such motifs. They are clustered close to the N terminus, downstream of a transmembrane (TM) domain and surround a Src homology region 3-binding module (2,4,6,14). The ICP10 PK activity is Mn 2ϩ ion-dependent, does not require monovalent cations, and is not inhibited by zinc sulfate, properties distinct from those of many cellular kinases such as casein kinase II (5). ICP10 is located on the cell surface and its PK activity is intrinsic. Mutants in which the TM domain or the conserved PK catalytic motifs were deleted or otherwise altered were rendered PK negative (4,5,7,8), and the PK activity of a chimeric protein consisting of ICP10 PK and the ligand-binding domain of the epidermal growth factor receptor was activated by epidermal growth factor (15). Most significantly, the ICP10 PK activity was ablated by mutation of the invarian...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

“…Northern blot hybridization was done exactly as described previously (8,28). The H11 probe was the 1.8-kilobase EcoRI/XhoI cDNA fragment.…”

Section: Construction Of Eukaryotic Expression Vectors For H11 and Thmentioning

confidence: 99%

Section: Construction Of Eukaryotic Expression Vectors For H11 and Thmentioning

confidence: 99%

See 2 more Smart Citations

A Novel Human Gene Similar to the Protein Kinase (PK) Coding Domain of the Large Subunit of Herpes Simplex Virus Type 2 Ribonucleotide Reductase (ICP10) Codes for a Serine-Threonine PK and Is Expressed in Melanoma Cells

Smith

Kulka

et al. 2000

Journal of Biological Chemistry

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128

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“…Most HSV-1 infections can be successfully treated with acyclovir and its derivatives; however, a large research effort is currently devoted to developing alternative treatment strategies to tackle drug-resistant strains of HSV-1. Among the new approaches to antiviral treatment, conventional antisense reagents (2,3) and ribozyme technology (4,5) are particularly promising. We decided to evaluate the potential for specific antiviral intervention at an alternative level: repression of transcription by customized zinc-finger transcription factors, as shown to be possible by Choo et al (6).…”

mentioning

confidence: 99%

Inhibition of herpes simplex virus 1 gene expression by designer zinc-finger transcription factors

Papworth

Moore

Isalan

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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The herpes simplex virus 1 (HSV-1) replicative cycle begins by binding of the viral activator, VP16, to a set of sequences in the immediate-early (IE) gene promoters. With the aim of inhibiting this cycle, we have constructed a number of synthetic zinc-finger DNA-binding peptides by using recently reported methods. Peptides containing either three or six fingers, targeted to a viral promoter, were engineered as fusions with a KOX-1 transcription repression domain. These proteins bound to the HSV-1 IE175k (ICP4) promoter, in vitro, with nanomolar or subnanomolar binding affinity. However, in a chloramphenicol acetyltransferase reporter system, only the six-finger protein was found to repress VP16-activated transcription significantly. Thus the longer array of zinc fingers is required to compete successfully against VP16, one of the most powerful natural activators known. We found that the HSV-1 replication cycle can be partially repressed by the six-finger peptide with the viral titer reduced by 90%.

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A Novel Gene Expressed in Human Keratinocytes with Long-Term In Vitro Growth Potential is Required for Cell Growth

Aurelian

Smith

Winchurch

et al. 2001

Journal of Investigative Dermatology

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The herpes simplex virus large subunit of ribonucleotide reductase differs from its counterparts in eukaryotic and prokaryotic cells and in other viruses in that it contains a unique domain that codes for a distinct serine-threonine protein kinase that activates the Ras/MEK/MAPK mitogenic pathway and is required for virus growth. Previous studies suggested that ribonucleotide reductase protein kinase was co-opted from a cellular gene. Cellular genes similar to ribonucleotide reductase protein kinase were not cloned, however, and their function is unknown. Here we report that a novel gene (H11) that codes for a protein similar to herpes simplex virus 2 ribonucleotide reductase protein kinase, is expressed in skin tissues, cultured keratinocytes, and the keratinocyte cell line A431. The protein is phosphorylated and it associates with the plasma membrane. H11 is expressed in keratinocytes with long-term in vitro growth potential and is coexpressed with high levels of adhesion molecules involved in signal transduction, such as beta1 integrin. Antisense oligonucleotides that inhibit H11 expression inhibit DNA synthesis and keratinocyte proliferation, suggesting that H11 expression is required for cell growth.

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Herpes Simplex Virus-Mediated Activation of Human Immunodeficiency Virus Is Inhibited by Oligonucleoside Methylphosphonates That Target Immediate-Early mRNAs 1 and 3

Cited by 7 publications

References 56 publications

A Novel Human Gene Similar to the Protein Kinase (PK) Coding Domain of the Large Subunit of Herpes Simplex Virus Type 2 Ribonucleotide Reductase (ICP10) Codes for a Serine-Threonine PK and Is Expressed in Melanoma Cells

A Novel Human Gene Similar to the Protein Kinase (PK) Coding Domain of the Large Subunit of Herpes Simplex Virus Type 2 Ribonucleotide Reductase (ICP10) Codes for a Serine-Threonine PK and Is Expressed in Melanoma Cells

Inhibition of herpes simplex virus 1 gene expression by designer zinc-finger transcription factors

A Novel Gene Expressed in Human Keratinocytes with Long-Term In Vitro Growth Potential is Required for Cell Growth

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