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Journal articles on the topic 'HSV-1 DNA polymerase'

Author: Grafiati

Published: 4 June 2021

Last updated: 1 February 2022

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1

Thomsen, Darrell R., Nancee L. Oien, Todd A. Hopkins, et al. "Amino Acid Changes within Conserved Region III of the Herpes Simplex Virus and Human Cytomegalovirus DNA Polymerases Confer Resistance to 4-Oxo-Dihydroquinolines, a Novel Class of Herpesvirus Antiviral Agents." Journal of Virology 77, no. 3 (2003): 1868–76. http://dx.doi.org/10.1128/jvi.77.3.1868-1876.2003.

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ABSTRACT The 4-oxo-dihydroquinolines (PNU-182171 and PNU-183792) are nonnucleoside inhibitors of herpesvirus polymerases (R. J. Brideau et al., Antiviral Res. 54:19-28, 2002; N. L. Oien et al., Antimicrob. Agents Chemother. 46:724-730, 2002). In cell culture these compounds inhibit herpes simplex virus type 1 (HSV-1), HSV-2, human cytomegalovirus (HCMV), varicella-zoster virus (VZV), and human herpesvirus 8 (HHV-8) replication. HSV-1 and HSV-2 mutants resistant to these drugs were isolated and the resistance mutation was mapped to the DNA polymerase gene. Drug resistance correlated with a poin

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2

Aduma, P. J., S. V. Gupta, and A. L. Stuart. "Interaction of 5-Methoxymethyl-2′-Deoxyuridine Triphosphate with DNA Polymerases: Effects of the 5-Substituent and Comparison with the Deoxycytidine Derivative." Antiviral Chemistry and Chemotherapy 3, no. 4 (1992): 243–47. http://dx.doi.org/10.1177/095632029200300406.

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5-Methoxymethyl-2′-deoxyuridine (MMdUrd) is a selective anti-herpes agent that is dependent upon initial phosphorylation by Herpes simplex virus-induced deoxythymidine kinase. In order to determine its mechanism of action, MMdUrd was converted to the 5′-triphosphate (MMdUTP) and the nature of interaction of MMdUTP and dTTP with DNA polymerase of E. coli, HSV-1, and human α was investigated. The order of utilization of deoxyuridine analogues by bacterial and HSV-1 DNA polymerases for DNA synthesis was: dTTP > MMdUTP. In contrast, 5-methoxymethyl-2′-deoxycytidine-5′-triphosphate (MMdCTP) was

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3

Zhu, Yali, Jason Stroud, Liping Song, and Deborah S. Parris. "Kinetic Approaches to Understanding the Mechanisms of Fidelity of the Herpes Simplex Virus Type 1 DNA Polymerase." Journal of Nucleic Acids 2010 (2010): 1–15. http://dx.doi.org/10.4061/2010/631595.

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We discuss how the results of presteady-state and steady-state kinetic analysis of the polymerizing and excision activities of herpes simplex virus type 1 (HSV-1) DNA polymerase have led to a better understanding of the mechanisms controlling fidelity of this important model replication polymerase. Despite a poorer misincorporation frequency compared to other replicative polymerases with intrinsic 3′to 5′exonuclease (exo) activity, HSV-1 DNA replication fidelity is enhanced by a high kinetic barrier to extending a primer/template containing a mismatch or abasic lesion and by the dynamic abilit

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4

Zhu, Yali, Zetang Wu, M. Cristina Cardoso, and Deborah S. Parris. "Processing of Lagging-Strand Intermediates In Vitro by Herpes Simplex Virus Type 1 DNA Polymerase." Journal of Virology 84, no. 15 (2010): 7459–72. http://dx.doi.org/10.1128/jvi.01875-09.

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ABSTRACT The processing of lagging-strand intermediates has not been demonstrated in vitro for herpes simplex virus type 1 (HSV-1). Human flap endonuclease-1 (Fen-1) was examined for its ability to produce ligatable products with model lagging-strand intermediates in the presence of the wild-type or exonuclease-deficient (exo−) HSV-1 DNA polymerase (pol). Primer/templates were composed of a minicircle single-stranded DNA template annealed to primers that contained 5′ DNA flaps or 5′ annealed DNA or RNA sequences. Gapped DNA primer/templates were extended but not significantly strand displaced

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5

Piret, Jocelyne, Nathalie Goyette, Brian E. Eckenroth, Emilien Drouot, Matthias Götte, and Guy Boivin. "Contrasting Effects of W781V and W780V Mutations in Helix N of Herpes Simplex Virus 1 and Human Cytomegalovirus DNA Polymerases on Antiviral Drug Susceptibility." Journal of Virology 89, no. 8 (2015): 4636–44. http://dx.doi.org/10.1128/jvi.03360-14.

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ABSTRACTDNA polymerases of theHerpesviridaeand bacteriophage RB69 belong to the α-like DNA polymerase family. In spite of similarities in structure and function, the RB69 enzyme is relatively resistant to foscarnet, requiring the mutation V478W in helix N to promote the closed conformation of the enzyme to make it susceptible to the antiviral. Here, we generated recombinant herpes simplex virus 1 (HSV-1) and human cytomegalovirus (HCMV) mutants harboring the revertant in UL30 (W781V) and UL54 (W780V) DNA polymerases, respectively, to further investigate the impact of this tryptophan on antivir

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6

Hassan, Sherif T. S., Miroslava Šudomová, Kateřina Berchová-Bímová, Karel Šmejkal, and Javier Echeverría. "Psoromic Acid, a Lichen-Derived Molecule, Inhibits the Replication of HSV-1 and HSV-2, and Inactivates HSV-1 DNA Polymerase: Shedding Light on Antiherpetic Properties." Molecules 24, no. 16 (2019): 2912. http://dx.doi.org/10.3390/molecules24162912.

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Psoromic acid (PA), a bioactive lichen-derived compound, was investigated for its inhibitory properties against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), along with the inhibitory effect on HSV-1 DNA polymerase, which is a key enzyme that plays an essential role in HSV-1 replication cycle. PA was found to notably inhibit HSV-1 replication (50% inhibitory concentration (IC50): 1.9 μM; selectivity index (SI): 163.2) compared with the standard drug acyclovir (ACV) (IC50: 2.6 μM; SI: 119.2). The combination of PA with ACV has led to potent inhibitory activity against HSV-1 replicatio

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7

Kamiyama, Tomoko, Masahiko Kurokawa, and Kimiyasu Shiraki. "Characterization of the DNA polymerase gene of varicella-zoster viruses resistant to acyclovir." Journal of General Virology 82, no. 11 (2001): 2761–65. http://dx.doi.org/10.1099/0022-1317-82-11-2761.

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The nucleotide changes of the DNA polymerase gene and the susceptibility of acyclovir (ACV)-resistant varicella-zoster virus (VZV) mutants to anti-herpetic drugs were determined and compared to those of herpes simplex virus type 1 (HSV-1) mutants. The seven ACV-resistant VZV mutants were classified into three groups, N779S, G805C and V855M, according to the sequences of their DNA polymerase genes. The amino acid substitutions N779S and G805C were identical in position to the N815S and G814C mutations in the HSV-1 DNA polymerase mutants, respectively, and the V855M amino acid substitution was s

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8

Oien, Nancee L., Roger J. Brideau, Todd A. Hopkins, et al. "Broad-Spectrum Antiherpes Activities of 4-Hydroxyquinoline Carboxamides, a Novel Class of Herpesvirus Polymerase Inhibitors." Antimicrobial Agents and Chemotherapy 46, no. 3 (2002): 724–30. http://dx.doi.org/10.1128/aac.46.3.724-730.2002.

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ABSTRACT Through broad screening of the compound library at Pharmacia, a naphthalene carboxamide was identified as a nonnucleoside inhibitor of human cytomegalovirus (HCMV) polymerase. Structure-activity relationship studies demonstrated that a quinoline ring could be substituted for naphthalene, resulting in the discovery of a 4-hydroxyquinoline-3-carboxamide (4-HQC) class of antiviral agents with unique biological properties. In vitro assays with the 4-HQCs have demonstrated potent inhibition of HCMV, herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV) polymerases but no in

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9

Danovich, R. M., and N. Frenkel. "Herpes simplex virus induces the replication of foreign DNA." Molecular and Cellular Biology 8, no. 8 (1988): 3272–81. http://dx.doi.org/10.1128/mcb.8.8.3272.

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Plasmids containing the simian virus 40 (SV40) DNA replication origin and the large T gene are replicated efficiently in Vero monkey cells but not in rabbit skin cells. Efficient replication of the plasmids was observed in rabbit skin cells infected with herpes simplex virus type 1 (HSV-1) and HSV-2. The HSV-induced replication required the large T antigen and the SV40 replication origin. However, it produced concatemeric molecules resembling replicative intermediates of HSV DNA and was sensitive to phosphonoacetate at concentrations known to inhibit the HSV DNA polymerase. Therefore, it invol

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10

Danovich, R. M., and N. Frenkel. "Herpes simplex virus induces the replication of foreign DNA." Molecular and Cellular Biology 8, no. 8 (1988): 3272–81. http://dx.doi.org/10.1128/mcb.8.8.3272-3281.1988.

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Plasmids containing the simian virus 40 (SV40) DNA replication origin and the large T gene are replicated efficiently in Vero monkey cells but not in rabbit skin cells. Efficient replication of the plasmids was observed in rabbit skin cells infected with herpes simplex virus type 1 (HSV-1) and HSV-2. The HSV-induced replication required the large T antigen and the SV40 replication origin. However, it produced concatemeric molecules resembling replicative intermediates of HSV DNA and was sensitive to phosphonoacetate at concentrations known to inhibit the HSV DNA polymerase. Therefore, it invol

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11

Burrel, Sonia, Claire Deback, Henri Agut, and David Boutolleau. "Genotypic Characterization of UL23 Thymidine Kinase and UL30 DNA Polymerase of Clinical Isolates of Herpes Simplex Virus: Natural Polymorphism and Mutations Associated with Resistance to Antivirals." Antimicrobial Agents and Chemotherapy 54, no. 11 (2010): 4833–42. http://dx.doi.org/10.1128/aac.00669-10.

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ABSTRACT The molecular mechanisms of herpes simplex virus (HSV) resistance to antiviral drugs interfering with viral DNA synthesis reported so far rely on the presence of mutations within UL23 (thymidine kinase [TK]) and UL30 (DNA polymerase) genes. The interpretation of genotypic antiviral resistance assay results requires the clear distinction between resistance mutations and natural interstrain sequence variations. The objectives of this work were to describe extensively the natural polymorphism of UL23 TK and UL30 DNA polymerase among HSV-1 and HSV-2 strains and the amino acid changes pote

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12

Lindborg, B. "Polymerase Domains of Human Immunodeficiency Virus Type 1 Reverse Transcriptase and Herpes Simplex Virus Type 1 DNA Polymerase: Their Predicted Three-Dimensional Structures and some Putative Functions in Comparison with E. Coli DNA Polymerase I. A Critical Survey." Antiviral Chemistry and Chemotherapy 3, no. 4 (1992): 223–41. http://dx.doi.org/10.1177/095632029200300405.

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Hypothetical three-dimensional models for the entire polymerase domain of HIV-1 reverse transcriptase (HIV RT) and conserved regions of HSV-1 DNA polymerase (HSV pol) were created, primarily from literature data on mutations and principles of protein structure, and compared with those of E. coli DNA polymerase I (E. coli pol I). The corresponding parts, performing similar functions, were found to be analogous, not homologous, in structure with different β topologies and sequential arrangement. The polymerase domain of HSV pol is shown to form an anti-parallel β-sheet with α-helices, but with a

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13

Ono, Nobukazu, Satoshi Iwayama, Katsuya Suzuki, et al. "Mode of Action of (1′S,2′R)-9-{[1′,2′-Bis(hydroxymethyl) cycloprop-1′-yl]methyl}guanine (A-5021) against Herpes Simplex Virus Type 1 and Type 2 and Varicella-Zoster Virus." Antimicrobial Agents and Chemotherapy 42, no. 8 (1998): 2095–102. http://dx.doi.org/10.1128/aac.42.8.2095.

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ABSTRACT The mode of action of (1′S,2′R)-9-{[1′,2′-bis(hydroxymethyl)cycloprop-1′-yl]methyl}guanine (A-5021) against herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus (VZV) was studied. A-5021 was monophosphorylated at the 2′ site by viral thymidine kinases (TKs). The 50% inhibitory values for thymidine phosphorylation of A-5021 by HSV-1 TK and HSV-2 TK were comparable to those for penciclovir (PCV) and lower than those for acyclovir (ACV). Of these three agents, A-5021 inhibited VZV TK most efficiently. A-5021 was phosphorylated to a mono-, di-, and triphosphate in MRC-5

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14

Saijo, Masayuki, Tatsuo Suzutani, Shigeru Morikawa, and Ichiro Kurane. "Genotypic Characterization of the DNA Polymerase and Sensitivity to Antiviral Compounds of Foscarnet-Resistant Herpes Simplex Virus Type 1 (HSV-1) Derived from a Foscarnet-Sensitive HSV-1 Strain." Antimicrobial Agents and Chemotherapy 49, no. 2 (2005): 606–11. http://dx.doi.org/10.1128/aac.49.2.606-611.2005.

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ABSTRACT Foscarnet is widely used for the treatment of acyclovir-resistant herpesvirus infections, and foscarnet-resistant herpesvirus infections are a serious concern in immunocompromised patients. Twenty-seven single-plaque isolates of herpes simplex virus type 1 (HSV-1) resistant to foscarnet were selected from foscarnet- and acyclovir-sensitive HSV-1 strain TAS by exposure to foscarnet, and the DNA polymerase genes were analyzed. The sensitivities of these mutants to foscarnet, cidofovir, S2242, acyclovir, ganciclovir, and penciclovir were determined. A single amino acid substitution, doub

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15

Burch, April D., and Sandra K. Weller. "Herpes Simplex Virus Type 1 DNA Polymerase Requires the Mammalian Chaperone Hsp90 for Proper Localization to the Nucleus." Journal of Virology 79, no. 16 (2005): 10740–49. http://dx.doi.org/10.1128/jvi.79.16.10740-10749.2005.

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ABSTRACT Many viruses and bacteriophage utilize chaperone systems for DNA replication and viral morphogenesis. We have previously shown that in the herpes simplex virus type 1 (HSV-1)-infected cell nucleus, foci enriched in the Hsp70/Hsp40 chaperone machinery are formed adjacent to viral replication compartments (A. D. Burch and S. K. Weller, J. Virol. 78:7175-7185, 2004). These foci have now been named virus-induced chaperone-enriched (VICE) foci. Since the Hsp90 chaperone machinery is known to engage the Hsp70/Hsp40 system in eukaryotes, the subcellular localization of Hsp90 in HSV-1-infecte

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16

Kuo, Yuh-Chi, Lie-Chwen Lin, Wei-Jern Tsai, Cheng-Jen Chou, Szu-Hao Kung, and Yen-Hui Ho. "Samarangenin B from Limonium sinense Suppresses Herpes Simplex Virus Type 1 Replication in Vero Cells by Regulation of Viral Macromolecular Synthesis." Antimicrobial Agents and Chemotherapy 46, no. 9 (2002): 2854–64. http://dx.doi.org/10.1128/aac.46.9.2854-2864.2002.

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ABSTRACT Inhibitory effects of ethanolic extracts from 10 Chinese herbs on herpes simplex virus type 1 (HSV-1) replication were investigated. By a bioassay-guided fractionation procedure, samarangenin B (Sam B) was isolated from Limonium sinense; Sam B significantly suppressed HSV-1 multiplication in Vero cells without apparent cytotoxicity. Time-of-addition experiments suggested that the inhibitory action of Sam B on HSV-1 replication was not due to the blocking of virus adsorption. In an attempt to further localize the point in the HSV-1 replication cycle where arrest occurred, a set of key

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17

Wilkinson, Dianna E., and Sandra K. Weller. "Inhibition of the Herpes Simplex Virus Type 1 DNA Polymerase Induces Hyperphosphorylation of Replication Protein A and Its Accumulation at S-Phase-Specific Sites of DNA Damage during Infection." Journal of Virology 79, no. 11 (2005): 7162–71. http://dx.doi.org/10.1128/jvi.79.11.7162-7171.2005.

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ABSTRACT The treatment of mammalian cells with genotoxic substances can trigger DNA damage responses that include the hyperphosphorylation of replication protein A (RPA), a protein that plays key roles in the recognition, signaling, and repair of damaged DNA. We have previously reported that in the presence of a viral polymerase inhibitor, herpes simplex virus type 1 (HSV-1) infection induces the hyperphosphorylation of RPA (D. E. Wilkinson and S. K. Weller, J. Virol. 78:4783-4796, 2004). We initiated the present study to further characterize this genotoxic response to HSV-1 infection. Here we

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Hill, James M., Melvyn J. Ball, Donna M. Neumann, et al. "The High Prevalence of Herpes Simplex Virus Type 1 DNA in Human Trigeminal Ganglia Is Not a Function of Age or Gender." Journal of Virology 82, no. 16 (2008): 8230–34. http://dx.doi.org/10.1128/jvi.00686-08.

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ABSTRACT The purpose of this study was to determine the presence and copy numbers of herpes simplex virus type 1 (HSV-1) DNA in human trigeminal ganglia (TG) with respect to age, gender, and postmortem interval (PMI). Human TG (n = 174, obtained from the Oregon Brain Bank, with data on age, gender, and PMI) were analyzed for HSV-1 DNA copies (HSV-1 DNA polymerase gene) by using real-time PCR. We found that 89.1% (131/147) of subjects and 90.1% (155/174) of TG contained HSV-1 DNA. The copy numbers of HSV-1 DNA in the positives ranged from very high (>106) to very low (5). These data confirm

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Lawler, Jessica L., and Donald M. Coen. "HSV-1 DNA polymerase 3′-5′ exonuclease-deficient mutant D368A exhibits severely reduced viral DNA synthesis and polymerase expression." Journal of General Virology 99, no. 10 (2018): 1432–37. http://dx.doi.org/10.1099/jgv.0.001138.

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Burgess, Robert C., James F. Bale, Leslie Michaels, and Richard J. H. Smith. "Polymerase Chain Reaction Amplification of Herpes Simplex Viral Dna from the Geniculate Ganglion of a Patient with Bell's Palsy." Annals of Otology, Rhinology & Laryngology 103, no. 10 (1994): 775–79. http://dx.doi.org/10.1177/000348949410301006.

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Bell's palsy is the most common cause of facial paralysis. In this study, we demonstrate the presence of herpes simplex viral type 1 (HSV-1) genomic DNA in the geniculate ganglion of a patient who had Bell's palsy. This association suggests that in this patient, HSV-1 may have caused Bell's palsy. If HSV-1 is a cause of Bell's palsy, treatment with acyclovir may be beneficial. Additional studies should be done to establish the prevalence of HSV-1 as an etiologic agent of Bell's palsy.

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Glauser, Daniel L., Regina Strasser, Andrea S. Laimbacher, et al. "Live Covisualization of Competing Adeno-Associated Virus and Herpes Simplex Virus Type 1 DNA Replication: Molecular Mechanisms of Interaction." Journal of Virology 81, no. 9 (2007): 4732–43. http://dx.doi.org/10.1128/jvi.02476-06.

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ABSTRACT We performed live cell visualization assays to directly assess the interaction between competing adeno-associated virus (AAV) and herpes simplex virus type 1 (HSV-1) DNA replication. Our studies reveal the formation of separate AAV and HSV-1 replication compartments and the inhibition of HSV-1 replication compartment formation in the presence of AAV. AAV Rep is recruited into AAV replication compartments but not into those of HSV-1, while the single-stranded DNA-binding protein HSV-1 ICP8 is recruited into both AAV and HSV-1 replication compartments, although with differential stainin

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22

Jaramillo, Nacarí, Esteban Domingo, María Carmen Muñoz-Egea, Enrique Tabarés, and Ignacio Gadea. "Evidence of Muller’s ratchet in herpes simplex virus type 1." Journal of General Virology 94, no. 2 (2013): 366–75. http://dx.doi.org/10.1099/vir.0.044685-0.

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Population bottlenecks can have major effects in the evolution of RNA viruses, but their possible influence in the evolution of DNA viruses is largely unknown. Genetic and biological variation of herpes simplex virus type 1 (HSV-1) has been studied by subjecting 23 biological clones of the virus to 10 plaque-to-plaque transfers. In contrast to large population passages, plaque transfers led to a decrease in replicative capacity of HSV-1. Two out of a total of 23 clones did not survive to the last transfer in 143 TK– cells. DNA from three genomic regions (DNA polymerase, glycoprotein gD and thy

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23

Zhu, Yali, Kelly S. Trego, Liping Song, and Deborah S. Parris. "3′ to 5′ Exonuclease Activity of Herpes Simplex Virus Type 1 DNA Polymerase Modulates Its Strand Displacement Activity." Journal of Virology 77, no. 18 (2003): 10147–53. http://dx.doi.org/10.1128/jvi.77.18.10147-10153.2003.

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ABSTRACT Using a minicircle DNA primer-template, the wild-type catalytic subunit of herpes simplex virus type 1 (HSV-1) DNA polymerase (pol) was shown to lack significant strand displacement activity with or without its processivity factor, UL42. However, an exonuclease-deficient (exo−) pol (D368A) was capable of slow strand displacement. Although UL42 increased the rate (2/s) and processivity of strand displacement by exo− pol, the rate was slower than that for gap-filling synthesis. High inherent excision rates on matched primer-templates and rapid idling-turnover (successive rounds of excis

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Diawara, Silman, Laurent Bélec, Ahmadou Dem, et al. "Low prevalences of HIV infection and HSV genital shedding in the general adult female population in Senegal." Journal of Infection in Developing Countries 9, no. 11 (2015): 1272–76. http://dx.doi.org/10.3855/jidc.6227.

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Introduction: Herpes simplex virus (HSV) is the main co-factor for heterosexual transmission of the human immunodeficiency virus (HIV) in sub-Saharan Africa, and could be involved in the dynamics of the HIV epidemic in Senegal. Methodology: Genital shedding of HSV was evaluated in adult females who had visited the provincial healthcare centres in Diass, Louga, and Kebemer in Senegal. Study subjects were interviewed by a healthcare worker for sociodemographic characteristics and sexual behavior, and HIV serology was offered. In addition, cervical secretion lavage samples were evaluated for HSV

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Yoneda, Julliane Diniz, Magaly Girão Albuquerque, Kátia Zaccur Leal, et al. "Docking of anti-HIV-1 oxoquinoline-acylhydrazone derivatives as potential HSV-1 DNA polymerase inhibitors." Journal of Molecular Structure 1074 (September 2014): 263–70. http://dx.doi.org/10.1016/j.molstruc.2014.05.081.

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Terrell, Shariya L., Jean M. Pesola, and Donald M. Coen. "Roles of conserved residues within the pre-NH2-terminal domain of herpes simplex virus 1 DNA polymerase in replication and latency in mice." Journal of General Virology 95, no. 4 (2014): 940–47. http://dx.doi.org/10.1099/vir.0.061903-0.

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The catalytic subunit of the herpes simplex virus 1 DNA polymerase (HSV-1 Pol) is essential for viral DNA synthesis and production of infectious virus in cell culture. While mutations that affect 5′–3′ polymerase activity have been evaluated in animal models of HSV-1 infection, mutations that affect other functions of HSV-1 Pol have not. In a previous report, we utilized bacterial artificial chromosome technology to generate defined HSV-1 pol mutants with lesions in the previously uncharacterized pre-NH2-terminal domain. We found that the extreme N-terminal 42 residues (deletion mutant polΔN43

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Nicolas, Armel, Nathalie Alazard-Dany, Coline Biollay, et al. "Identification of Rep-Associated Factors in Herpes Simplex Virus Type 1-Induced Adeno-Associated Virus Type 2 Replication Compartments." Journal of Virology 84, no. 17 (2010): 8871–87. http://dx.doi.org/10.1128/jvi.00725-10.

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ABSTRACT Adeno-associated virus (AAV) is a human parvovirus that replicates only in cells coinfected with a helper virus, such as adenovirus or herpes simplex virus type 1 (HSV-1). We previously showed that nine HSV-1 factors are able to support AAV rep gene expression and genome replication. To elucidate the strategy of AAV replication in the presence of HSV-1, we undertook a proteomic analysis of cellular and HSV-1 factors associated with Rep proteins and thus potentially recruited within AAV replication compartments (AAV RCs). This study resulted in the identification of approximately 60 ce

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Herdewijn, P. A. M. M. "5-Substituted-2′-deoxyuridines as anti-HSV-1 Agents: Synthesis and Structure Activity Relationship." Antiviral Chemistry and Chemotherapy 5, no. 3 (1994): 131–46. http://dx.doi.org/10.1177/095632029400500301.

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Nucleoside and pyrophosphate analogues are currently in use to treat infection with Human herpesvirus 1 (HSV-1). Both series of compounds exert their activity by inhibition of the viral DNA polymerase either directly, or after anabolic phosphorylation. As the X-ray structure of the viral-specific DNA polymerase is not known, it is difficult to design a nucleoside or non-nucleoside antiviral agent which specifically inhibits this enzyme. Therefore, alternative strategies have relied on extensive structure activity relationship studies of anti-HSV-1 agents in an endeavour to understand the essen

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Artusi, Sara, Emanuela Ruggiero, Matteo Nadai, et al. "Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1." Viruses 13, no. 2 (2021): 196. http://dx.doi.org/10.3390/v13020196.

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The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed b

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Tian, Wang, Ying T. Hwang, Qiangsheng Lu, and Charles B. C. Hwang. "Finger Domain Mutation Affects Enzyme Activity, DNA Replication Efficiency, and Fidelity of an Exonuclease-Deficient DNA Polymerase of Herpes Simplex Virus Type 1." Journal of Virology 83, no. 14 (2009): 7194–201. http://dx.doi.org/10.1128/jvi.00632-09.

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ABSTRACT The catalytic subunit of herpes simplex virus DNA polymerase (Pol), a member of the B family polymerases, possesses both polymerase and exonuclease activities. We previously demonstrated that a recombinant virus (YD12) containing a double mutation within conserved exonuclease motif III of the Pol was highly mutagenic and rapidly evolved to contain an additional leucine-to-phenylalanine mutation at residue 774 (L774F), which is located within the finger subdomain of the polymerase domain. We further demonstrated that the recombinant L774F virus replicated DNA with increased fidelity an

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Bestman-Smith, Julie, and Guy Boivin. "Drug Resistance Patterns of Recombinant Herpes Simplex Virus DNA Polymerase Mutants Generated with a Set of Overlapping Cosmids and Plasmids." Journal of Virology 77, no. 14 (2003): 7820–29. http://dx.doi.org/10.1128/jvi.77.14.7820-7829.2003.

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ABSTRACT Herpes simplex virus (HSV) DNA polymerase (Pol) mutations can confer resistance to all currently available antiherpetic drugs. However, discrimination between mutations responsible for drug resistance and those that are part of viral polymorphism can be difficult with current methodologies. A new system is reported for rapid generation of recombinant HSV type 1 (HSV-1) DNA Pol mutants based on transfection of a set of overlapping viral cosmids and plasmids. With this approach, twenty HSV-1 recombinants with single or dual mutations within the DNA pol gene were successfully generated a

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Gupta, V. S., P. J. Aduma, Z. Jia, et al. "Relationship between Conformation and Antiviral Activity-II. 5-Methoxymethyl-2′-deoxycytidine and 5-methoxymethyl-N4-methyl-2′-deoxycytidine." Antiviral Chemistry and Chemotherapy 3, no. 1 (1992): 15–22. http://dx.doi.org/10.1177/095632029200300103.

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5-methoxymethyl-N4-methyl-2′-deoxycytidine (N4-Me-MMdCyd) and 5-methoxymethyl-N4-methyl-2′-deoxycytidine-5′-monophosphate (N4-Me-MMdCMP) were synthesized to confer resistance to deamination by deaminating enzymes. N4-Me-MMdCyd and N4-Me-MMdCMP were inactive against Herpes simplex virus type 1 (HSV-1) and also nontoxic to VERO cells up to 1796 μM (highest concentration tested). 5-methoxymethyl-2′-deoxycytidine-5′-monophosphate (MMdCMP) was more potent than the nucleoside against HSV-1 in VERO cells. In HSV-infected VERO cells (10 PFU/cell), N4-Me-MMdCyd caused only slight perturbations of deoxy

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Jia, William W. G., Jiren Tan, Gary J. Redekop, and James H. Goldie. "Toxicity studies in thymidine kinase—deficient herpes simplex virus therapy for malignant astrocytoma." Journal of Neurosurgery 85, no. 4 (1996): 662–66. http://dx.doi.org/10.3171/jns.1996.85.4.0662.

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✓ Previous studies have shown that genetically engineered thymidine kinase (tk)—defective herpes simplex virus type 1 (HSV-1) can effectively and selectively destroy gliomas in animal models. The consequences of viral infection and tumor regression must be characterized before this therapy can be applied in human trials. To study the potential for long-term toxicity, immunocompetent rats harboring 9L gliosarcomas were injected intratumorally with a tk—defective HSV-1, KOS-SB, at titers that previously have been demonstrated to cause tumor regression. In animals surviving 3 months or longer fol

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Avila, Emiliana Claro, Fabiana Finger-Jardim, Carla Vitola Gonçalves, Vanusa Pousada da Hora, Marcelo Alves Soares, and Ana Maria Barral de Martínez. "High Incidence of Herpes Simplex Virus-1 in Cord Blood and Placenta Infection of Women in Southern Brazil." Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics 42, no. 01 (2020): 005–11. http://dx.doi.org/10.1055/s-0039-1700794.

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Abstract Objective Estimate the prevalence of human herpesvirus type 1 HSV-1 DNA in placental samples, its incidence in umbilical cord blood of newborns and the associated risk factors. Methods Placental biopsies and umbilical cord blood were analyzed, totaling 480 samples, from asymptomatic parturients and their newborns at a University Hospital. Nested polymerase chain reaction (PCR) and gene sequencing were used to identify the virus; odds ratio (OR) and relative risk (RR) were performed to compare risk factors associated with this condition. Results The prevalence of HSV-1 DNA in placental

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Kessler, Harald H., Gerhard Mühlbauer, Beate Rinner, et al. "Detection of Herpes Simplex Virus DNA by Real-Time PCR." Journal of Clinical Microbiology 38, no. 7 (2000): 2638–42. http://dx.doi.org/10.1128/jcm.38.7.2638-2642.2000.

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Molecular detection of herpes simplex virus (HSV) DNA is recognized as the reference standard assay method for the sensitive and specific diagnosis of central nervous system infections caused by HSV. In this study, a molecular assay based on real-time PCR on the LightCycler (LC) instrument was evaluated and compared with a home-brew molecular assay. The detection limit of the LC assay was determined with 10-fold dilutions of plasmid pS4 with the SalI restriction fragment of the DNA polymerase gene and with the First European Union Concerted Action HSV Proficiency Panel. A total of 59 cerebrosp

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Chen, Yan, Christine M. Livingston, Stacy D. Carrington-Lawrence, Ping Bai, and Sandra K. Weller. "A Mutation in the Human Herpes Simplex Virus Type 1 UL52 Zinc Finger Motif Results in Defective Primase Activity but Can Recruit Viral Polymerase and Support Viral Replication Efficiently." Journal of Virology 81, no. 16 (2007): 8742–51. http://dx.doi.org/10.1128/jvi.00174-07.

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ABSTRACT Herpes simplex virus type 1 (HSV-1) encodes a heterotrimeric helicase/primase complex consisting of UL5, UL8, and UL52. UL5 contains conserved helicase motifs, while UL52 contains conserved primase motifs, including a zinc finger motif. Although HSV-1 and HSV-2 UL52s contain a leucine residue at position 986, most other herpesvirus primase homologues contain a phenylalanine at this position. We constructed an HSV-1 UL52 L986F mutation and found that it can complement a UL52 null virus more efficiently than the wild type (WT). We thus predicted that the UL5/8/52 complex containing the

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Smirnova, D. I., O. A. Petrusha, A. V. Gracheva, E. A. Volynskaya, V. V. Zverev, and E. B. Faizuloev. "Rapid diagnostics of genital herpes by loop-mediated isothermal amplification method with fluorescent detection." Journal of microbiology epidemiology immunobiology, no. 6 (December 16, 2019): 40–46. http://dx.doi.org/10.36233/0372-9311-2019-6-40-46.

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Introduction. Due to the high clinical significance of herpesvirus diseases, the searching of fast and effective methods for their diagnosis remains relevant.The aim of the study was to evaluate the diagnostic efficiency of the loop-mediated isothermal amplification of DNA with real-time fluorescent detection (RT-LAMP) with SYTO-82 dye on a model of herpes simplex virus (HSV) infection.Materials and methods. A total of 44 urogenital swabs containing type 1 and type 2 HSV DNA and 43 swabs without HSV DNA, including 33 samples containing the DNA of cytomegalovirus, Epstein-Barr virus and herpesv

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Murakami, Shingo, Naohito Hato, Takashi Doi, Mutsuhiko Mizobuchi, and Naoaki Yanagihara. "Role of Herpes Simplex Virus Infection in the Pathogenesis of Facial Paralysis in Mice." Annals of Otology, Rhinology & Laryngology 105, no. 1 (1996): 49–53. http://dx.doi.org/10.1177/000348949610500108.

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To clarify the role and site of herpes simplex virus (HSV) infection in the pathogenesis of facial paralysis, we examined the viral genome by the polymerase chain reaction and the neutralization antibody titer using microplates in an animal model. Following inoculation with HSV type 1 of the KOS strain into mouse auricles, HSV DNA appeared in the ipsilateral facial nerve on the 3rd day, and in bilateral facial nerves and the brain stem on the 10th day only in animals with facial paralysis. In animals without facial paralysis, no HSV DNA was detected in these tissues. The neutralization antibod

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Millet, Rachel, Nelly Jolinon, Xuan-Nhi Nguyen, et al. "Impact of the MRN Complex on Adeno-Associated Virus Integration and Replication during Coinfection with Herpes Simplex Virus 1." Journal of Virology 89, no. 13 (2015): 6824–34. http://dx.doi.org/10.1128/jvi.00171-15.

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ABSTRACTAdeno-associated virus (AAV) is a helper-dependent parvovirus that requires coinfection with adenovirus (AdV) or herpes simplex virus 1 (HSV-1) to replicate. In the absence of the helper virus, AAV can persist in an episomal or integrated form. Previous studies have analyzed the DNA damage response (DDR) induced upon AAV replication to understand how it controls AAV replication. In particular, it was shown that the Mre11-Rad50-Nbs1 (MRN) complex, a major player of the DDR induced by double-stranded DNA breaks and stalled replication forks, could negatively regulate AdV and AAV replicat

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Wilkinson, Dianna E., and Sandra K. Weller. "Recruitment of Cellular Recombination and Repair Proteins to Sites of Herpes Simplex Virus Type 1 DNA Replication Is Dependent on the Composition of Viral Proteins within Prereplicative Sites and Correlates with the Induction of the DNA Damage Response." Journal of Virology 78, no. 9 (2004): 4783–96. http://dx.doi.org/10.1128/jvi.78.9.4783-4796.2004.

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ABSTRACT Herpes simplex virus type 1 (HSV-1) DNA replication is associated with nuclear domains called ND10, which contain host recombination proteins such as RPA, RAD51, and NBS1 and participate in the cell's response to DNA damage. The stages of HSV-1 infection have been described previously. Infected cells at stage IIIa are observed after the initial disruption of ND10 and display nuclear foci, or prereplicative sites, containing the viral single-stranded-DNA-binding protein (UL29), the origin-binding protein (UL9), and the heterotrimeric helicase-primase. At stage IIIb, the viral polymeras

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Barrera, I., D. Bloom, and M. Challberg. "An Intertypic Herpes Simplex Virus Helicase-Primase Complex Associated with a Defect in Neurovirulence Has Reduced Primase Activity." Journal of Virology 72, no. 2 (1998): 1203–9. http://dx.doi.org/10.1128/jvi.72.2.1203-1209.1998.

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ABSTRACT R13-1 is an intertypic recombinant virus in which the left-hand 18% of the herpes simplex virus type 1 (HSV-1) genome is replaced by homologous sequences from HSV-2. R13-1 is nonneurovirulent and defective in DNA replication in neurons. The defect was localized to the UL5 open reading frame by using marker rescue analysis (D. C. Bloom and J. G. Stevens, J. Virol. 68:3761–3772, 1994). To provide conclusive evidence that UL5 is the only HSV-2 gene involved in the restricted replication phenotype of R13-1, we have characterized the phenotype of a recombinant virus (IB1) in which only the

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Kubat, Nicole J., Robert K. Tran, Peterjon McAnany, and David C. Bloom. "Specific Histone Tail Modification and Not DNA Methylation Is a Determinant of Herpes Simplex Virus Type 1 Latent Gene Expression." Journal of Virology 78, no. 3 (2004): 1139–49. http://dx.doi.org/10.1128/jvi.78.3.1139-1149.2004.

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ABSTRACT During herpes simplex virus type 1 (HSV-1) latency, gene expression is tightly repressed except for the latency-associated transcript (LAT). The mechanistic basis for this repression is unknown, but its global nature suggests regulation by an epigenetic mechanism such as DNA methylation. Previous work demonstrated that latent HSV-1 genomes are not extensively methylated, but these studies lacked the resolution to examine methylation of individual CpGs that could repress transcription from individual promoters during latency. To address this point, we employed established models to pre

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Piret, Jocelyne, Nathalie Goyette, and Guy Boivin. "Novel Method Based on Real-Time Cell Analysis for Drug Susceptibility Testing of Herpes Simplex Virus and Human Cytomegalovirus." Journal of Clinical Microbiology 54, no. 8 (2016): 2120–27. http://dx.doi.org/10.1128/jcm.03274-15.

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The plaque reduction assay (PRA) is the gold standard phenotypic method to determine herpes simplex virus (HSV) and human cytomegalovirus (HCMV) susceptibilities to antiviral drugs. However, this assay is subjective and labor intensive. Here, we describe a novel antiviral phenotypic method based on real-time cell analysis (RTCA) that measures electronic impedance over time. The effective drug concentrations that reduced by 50% (EC50s) the cytopathic effects induced by HSV-1 and HCMV were evaluated by both methods. The EC50s of acyclovir and foscarnet against a reference wild-type (WT) HSV-1 st

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Suzutani, Tatsuo, Ken Ishioka, Erik De Clercq, et al. "Differential Mutation Patterns in Thymidine Kinase and DNA Polymerase Genes of Herpes Simplex Virus Type 1 Clones Passaged in the Presence of Acyclovir or Penciclovir." Antimicrobial Agents and Chemotherapy 47, no. 5 (2003): 1707–13. http://dx.doi.org/10.1128/aac.47.5.1707-1713.2003.

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ABSTRACT A total of 21 clones of acyclovir (ACV)-resistant (ACVr) herpes simplex virus type 1 (HSV-1) and 23 clones of penciclovir (PCV)-resistant (PCVr) HSV-1, emerging during serial passages in the presence of ACV or PCV, were isolated under conditions excluding contamination of resistant mutants in the starting virus culture, and their mutations in the thymidine kinase (TK) and DNA polymerase (DNA Pol) genes were analyzed comparatively. Mutations in the TK genes from ACVr mutants consisted of 50% single nucleotide substitutions and 50% frameshift mutations, while the corresponding figures f

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Martina Lefaan, Yannie Febby, and Riani Setiadhi. "THYMIDINE KINASE AS A CAUSATIVE FACTOR FOR TYPE 1 HERPES SIMPLEX VIRUS RESISTANCE AGAINST ACYCLOVIR." Dentino : Jurnal Kedokteran Gigi 5, no. 2 (2020): 159. http://dx.doi.org/10.20527/dentino.v5i2.8954.

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ABSTRACTBackground: Herpes Simplex Virus (HSV) infection demonstrates a high prevalence in the world. Acyclovir, one of guanine synthetic analogues, is commonly used to treat infections caused by HSV. HSV resistance against acyclovir may occur, especially in immunocompromised and immunocompetent patients, as the consequence of viral mutations. Thymidine kinase (TK) is an HSV tegument protein which plays an important role in HSV-1 resistance against acyclovir. Purpose: The purpose of this article is to review the mechanisms of TK mutation that cause HSV-1 resistance against acyclovir. Review: A

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Matic-Petrovic, Sanja, Ksenija Zelic, Jelena Milasin, Branka Popovic, Ana Pucar, and Obrad Zelic. "Detection of herpes simplex virus type 1 in gingival crevicular fluid of gingival sulcus/periodontal pocket using polymerase chain reaction." Srpski arhiv za celokupno lekarstvo 142, no. 5-6 (2014): 296–300. http://dx.doi.org/10.2298/sarh1406296m.

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Introduction. Pathogenesis and some characteristics of periodontitis cannot be fully explained by bacterial etiology alone. Herpes viruses may bridge the gap between clinical characteristics and molecular understanding of periodontal destruction. Objective. The aim of this study was to investigate the prevalence of herpes simplex virus type 1 (HSV-1) in gingival crevicular fluid (GCF) of healthy and damaged periodontium in Serbian population and to explore potential correlation between the presence of this virus and the level of periodontal destruction. Methods. Samples were collected from gin

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VERRI, Annalisa, Federico FOCHER, Richard J. DUNCOMBE, et al. "Anti-(herpes simplex virus) activity of 4′-thio-2′-deoxyuridines: a biochemical investigation for viral and cellular target enzymes." Biochemical Journal 351, no. 2 (2000): 319–26. http://dx.doi.org/10.1042/bj3510319.

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The antiviral activity of several nucleoside analogues is often limited by their rapid degradation by pyrimidine nucleoside phosphorylases. In an attempt to avoid this degradation, several modified nucleosides have been synthesized. A series of 4´-thio-2´-deoxyuridines exhibits an anti-[herpes simplex virus (HSV)] activity significantly higher (20–600 times) than that shown by the corresponding 4´-oxy counterpart. We investigated the mode of action of these compounds and we found that: (i) several 4´-thio-2´-deoxyuridines are phosphorylated to the mono- and di-phosphates by HSV-1 thymidine kin

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Zhou, Changhong, and David M. Knipe. "Association of Herpes Simplex Virus Type 1 ICP8 and ICP27 Proteins with Cellular RNA Polymerase II Holoenzyme." Journal of Virology 76, no. 12 (2002): 5893–904. http://dx.doi.org/10.1128/jvi.76.12.5893-5904.2002.

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ABSTRACT Herpes simplex virus 1 (HSV-1) infection causes the shutoff of host gene transcription and the induction of a transcriptional program of viral gene expression. Cellular RNA polymerase II is responsible for transcription of all the viral genes, but several viral proteins stimulate viral gene transcription. ICP4 is required for all delayed-early and late gene transcription, ICP0 stimulates transcription of viral genes, and ICP27 stimulates expression of some early genes and transcription of at least some late viral genes. The early DNA-binding protein, ICP8, also stimulates late gene tr

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DA SILVA, Samya Jezine, Mauro Jorge CABRAL-CASTRO, Maria Angélica GUIMARÃES, José Mauro PERALTA, and Marzia PUCCIONI-SOHLER. "Cerebrospinal fluid challenges for the diagnosis of herpes simplex infection in the central nervous system." Arquivos de Neuro-Psiquiatria 78, no. 3 (2020): 163–68. http://dx.doi.org/10.1590/0004-282x20190179.

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Abstract Herpes simplex virus (HSV) is a cause of a severe disease of the central nervous system (CNS) in humans. The demonstration of specific antibodies in the cerebrospinal fluid (CSF) may contribute to the retrospective neurological diagnosis. However, the commercial immunological tests for HSV infection are for use in serum samples. Objective: The aim of the present study was to adapt a commercial kit anti-HSV IgG used for serum samples to be performed with a CSF sample. Methods: Forty CSF specimens from 38 patients with suspected CNS HSV infection were serially diluted for detecting anti

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Obisesan, Oluwafemi Samuel, Nomathamsanqa Patricia Sithebe, and Hazel Tumelo Mufhandu. "Seroprevalence and characterisation of herpes simplex virus from human immunodeficiency virus in samples collected from the North-West and KwaZulu-Natal Provinces: a retrospective study." F1000Research 10 (February 11, 2021): 105. http://dx.doi.org/10.12688/f1000research.28105.1.

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Background: Herpes simplex viruses (HSVs) are highly pervasive and show a strong synergistic interaction with human immunodeficiency virus (HIV). High prevalence of HSV type 1 (HSV-1) has been reported in Africa with a prevalence rate of 20-80% in women and 10-50% in men. Studies on the prevalence of HSV in South Africa are few considering the rate of HIV infection in the country. Our focus was to determine the molecular prevalence of HSV-DNA in HIV-1 sera. Methods: In total, 44 convenience samples were screened for HSV and HIV-1 using the highly sensitive enzyme-linked immunosorbent assay (EL

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