The Experts below are selected from a list of 90 Experts worldwide ranked by ideXlab platform

Ronald S. Goldstein - One of the best experts on this subject based on the ideXlab platform.

  • Varicella-Zoster Virus (VZV) Small Noncoding RNAs Antisense to the VZV Latency-Encoded Transcript VLT Enhance Viral Replication.
    Journal of virology, 2020
    Co-Authors: Punam Bisht, Biswajit Das, Paul R. Kinchington, Ronald S. Goldstein
    Abstract:

    Small noncoding RNAs (sncRNA), including microRNA (miR), are expressed by many viruses to provide an additional layer of gene expression regulation. Our work has shown that varicella-zoster virus (VZV; also called Human Herpesvirus 3 [HHV3]), the Human alphaHerpesvirus causing varicella and herpes zoster, expresses 24 virally encoded sncRNA (VZVsncRNA) in infected cells. Here, we demonstrate that several VZVsncRNA can modulate VZV growth, including four VZVsncRNA (VZVsncRNA10, -11, -12, and -13) that are antisense to VLT, a transcript made in lytic infections and associated with VZV latency. The influence on productive VZV growth and spread was assessed in epithelial cells transfected with locked nucleotide analog antagonists (LNAA). LNAA to the four VZVsncRNA antisense to VLT significantly reduced viral spread and progeny titers of infectious virus, suggesting that these sncRNA promoted lytic infection. The LNAA to VZVsncRNA12, encoded in the leader to ORF61, also significantly increased the levels of VLT transcripts. Conversely, overexpression of VZVsncRNA13 using adeno-associated virus consistently increased VZV spread and progeny titers. These results suggest that sncRNA antisense to VZV may regulate VZV growth, possibly by affecting VLT expression. Transfection of LNAA to VZVsncRNA14 and VZVsncRNA9 decreased and increased VZV growth, respectively, while LNAA to three other VZVsncRNA had no significant effects on replication. These data strongly support the conclusion that VZV replication is modulated by multiple virally encoded sncRNA, revealing an additional layer of complexity of VZV regulation of lytic infections. This may inform the development of novel anti-sncRNA-based therapies for treatment of VZV diseases.IMPORTANCE Varicella-zoster virus (VZV) causes herpes zoster, a major health issue in the aging and immunocompromised populations. Small noncoding RNAs (sncRNA) are recognized as important actors in modulating gene expression. This study extends our previous work and shows that four VZVsncRNA clustering in and near ORF61 and antisense to the latency-associated transcript of VZV can positively influence productive VZV infection. The ability of multiple exogenous small oligonucleotides targeting VZVsncRNA to inhibit VZV replication strengthens the possibility that they may inform development of novel treatments for painful herpes zoster.

  • Varicella-Zoster Virus Expresses Multiple Small Noncoding RNAs.
    Journal of virology, 2017
    Co-Authors: Amos Markus, Paul R. Kinchington, Linoy Golani, Nishant Kumar Ojha, Tatiana Borodiansky-shteinberg, Ronald S. Goldstein
    Abstract:

    Many Herpesviruses express small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), that may play roles in regulating lytic and latent infections. None have yet been reported in varicella-zoster virus (VZV; also known as Human Herpesvirus 3 [HHV-3]). Here we analyzed next-generation sequencing (NGS) data for small RNAs in VZV-infected fibroblasts and Human embryonic stem cell-derived (hESC) neurons. Two independent bioinformatics analyses identified more than 20 VZV-encoded 20- to 24-nucleotide RNAs, some of which are predicted to have stem-loop precursors potentially representing miRNAs. These sequences are perfectly conserved between viruses from three clades of VZV. One NGS-identified sequence common to both bioinformatics analyses mapped to the repeat regions of the VZV genome, upstream of the predicted promoter of the immediate early gene open reading frame 63 (ORF63). This miRNA candidate was detected in each of 3 independent biological repetitions of NGS of RNA from fibroblasts and neurons productively infected with VZV using TaqMan quantitative PCR (qPCR). Importantly, transfected synthetic RNA oligonucleotides antagonistic to the miRNA candidate significantly enhanced VZV plaque growth rates. The presence of 6 additional small noncoding RNAs was also verified by TaqMan qPCR in productively infected fibroblasts and ARPE19 cells. Our results show VZV, like other Human Herpesviruses, encodes several sncRNAs and miRNAs, and some may regulate infection of host cells.IMPORTANCE Varicella-zoster virus is an important Human pathogen, with herpes zoster being a major health issue in the aging and immunocompromised populations. Small noncoding RNAs (sncRNAs) are recognized as important actors in modulating gene expression, and this study demonstrates the first reported VZV-encoded sncRNAs. Many are clustered to a small genomic region, as seen in other Human Herpesviruses. At least one VZV sncRNA was expressed in productive infection of neurons and fibroblasts that is likely to reduce viral replication. Since sncRNAs have been suggested to be potential targets for antiviral therapies, identification of these molecules in VZV may provide a new direction for development of treatments for painful herpes zoster.

D J Jeffries - One of the best experts on this subject based on the ideXlab platform.

  • Molecular biology of varicella-zoster virus. A review prepared for the UK Advisory Group on Chickenpox.
    The Journal of infection, 1998
    Co-Authors: D R Harper, R L Gilbert, D J Jeffries
    Abstract:

    Varicella-zoster virus (Human Herpesvirus 3; VZV) is one of eight herpes viruses that routinely infect Humans. It is classified as a member of the genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae. Of the other Human herpes viruses it is most closely related to the herpes simplex viruses (also members of the Alphalerpesvirinae). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar membrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.

  • Molecular Biology of Varicella-zoster Virus: A review prepared for the UK Advisory Group on Chickenpox
    Journal of Infection, 1998
    Co-Authors: D R Harper, R L Gilbert, D J Jeffries
    Abstract:

    Varicella-zoster virus (Human Herpesvirus 3; VZVI is one of eight viruses that routinely infect Humans. It is classified as a member of the genus Varicellovirus , subfamily Alphaherpesvirinae , family Herpesviridae . Of the other Human herpes viruses it is ost closely related to the herpes simplex viruses (also members of the Alphaherpesvirinae ). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar memhbrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.

  • Antiviral activity of 2-hydroxy fatty acids
    Antiviral Chemistry and Chemotherapy, 1996
    Co-Authors: David R. Harper, R L Gilbert, T. J. O'connor, D. Kinchington, N. Mahmood, R. A. J. Mcllhinney, D J Jeffries
    Abstract:

    Following an earlier demonstration of an antiviral effect against varicella-zoster virus (VZV, Human Herpesvirus 3) using 2-hydroxymyristic acid (2-hydroxy-tetradecanoic acid; 2-HM), an inhibitor of protein myristoylation, both 2-HM and 2-hydroxypalmitic acid (2-hydroxyhexadecanoic acid; 2-HP) have been tested against a range of viruses. Although both compounds inhibit the replication of varicella-zoster virus (VZV; Human Herpesvirus 3) they do not inhibit the replication of closely related Herpesviruses. They do, however, inhibit the replication of both poliovirus (a member of the Picornaviridae) and the Human immunodeficiency virus type 1 (HIV-1; a member of the Retroviridae). Neither compound is toxic to adherent cells by dye uptake assay, although limited toxicity is apparent to non-adherent cell lines at high concentrations. The mechanisms underlying these effects are discussed. A diminished effect of 2-hydroxymyristic acid when the compound is dissolved in dimethyl sulphoxide (DMSO) rather than ethanol is reported, and the implications for the use of DMSO as a 'universal solvent' for compound screening noted. Finally, it is suggested that targeting of 'virus-essential' cellular functions may provide an alternative route for inhibiting viral replication.

  • Effect of Inhibitors of Protein Myristoylation on Varicella-Zoster Virus Replication
    Antiviral Chemistry and Chemotherapy, 1994
    Co-Authors: R L Gilbert, D J Jeffries, David R. Harper, C. J. Blunt, R. A. J. Mcllhinney
    Abstract:

    Inhibitors of N-myristoyltransferase (NMT) have been shown to inhibit retrovirus replication, notably that of the Human immunodeficiency virus (HIV), where the absence of protein myristoylation inhibits viral replication. The authors have assayed 14 compounds derived from myristic acid for activity against varicella-zoster virus (Human Herpesvirus 3; VZV) by plaque reduction assay. Seven showed cytotoxicity and of the others, two failed to inhibit VZV replication. One of these was N-myristoylglycinaldiethylacetal (GoA), which has been reported to be active against HIV. 12-(methoxy) dodecanoic acid (13-oxamyristic acid), which has also been reported to inhibit HIV replication, was found to inhibit VZV replication but was cytotoxic at high concentrations. The greatest inhibitory effect without apparent toxicity was induced by 2-hydroxytetradecanoic acid and its enantiomers. The results of these assays provide further evidence that inhibitors of NMT have potential as antiviral agents against the many viruses...

D R Harper - One of the best experts on this subject based on the ideXlab platform.

  • Molecular biology of varicella-zoster virus. A review prepared for the UK Advisory Group on Chickenpox.
    The Journal of infection, 1998
    Co-Authors: D R Harper, R L Gilbert, D J Jeffries
    Abstract:

    Varicella-zoster virus (Human Herpesvirus 3; VZV) is one of eight herpes viruses that routinely infect Humans. It is classified as a member of the genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae. Of the other Human herpes viruses it is most closely related to the herpes simplex viruses (also members of the Alphalerpesvirinae). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar membrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.

  • Molecular Biology of Varicella-zoster Virus: A review prepared for the UK Advisory Group on Chickenpox
    Journal of Infection, 1998
    Co-Authors: D R Harper, R L Gilbert, D J Jeffries
    Abstract:

    Varicella-zoster virus (Human Herpesvirus 3; VZVI is one of eight viruses that routinely infect Humans. It is classified as a member of the genus Varicellovirus , subfamily Alphaherpesvirinae , family Herpesviridae . Of the other Human herpes viruses it is ost closely related to the herpes simplex viruses (also members of the Alphaherpesvirinae ). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar memhbrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.

Paul R. Kinchington - One of the best experts on this subject based on the ideXlab platform.

  • Varicella-Zoster Virus (VZV) Small Noncoding RNAs Antisense to the VZV Latency-Encoded Transcript VLT Enhance Viral Replication.
    Journal of virology, 2020
    Co-Authors: Punam Bisht, Biswajit Das, Paul R. Kinchington, Ronald S. Goldstein
    Abstract:

    Small noncoding RNAs (sncRNA), including microRNA (miR), are expressed by many viruses to provide an additional layer of gene expression regulation. Our work has shown that varicella-zoster virus (VZV; also called Human Herpesvirus 3 [HHV3]), the Human alphaHerpesvirus causing varicella and herpes zoster, expresses 24 virally encoded sncRNA (VZVsncRNA) in infected cells. Here, we demonstrate that several VZVsncRNA can modulate VZV growth, including four VZVsncRNA (VZVsncRNA10, -11, -12, and -13) that are antisense to VLT, a transcript made in lytic infections and associated with VZV latency. The influence on productive VZV growth and spread was assessed in epithelial cells transfected with locked nucleotide analog antagonists (LNAA). LNAA to the four VZVsncRNA antisense to VLT significantly reduced viral spread and progeny titers of infectious virus, suggesting that these sncRNA promoted lytic infection. The LNAA to VZVsncRNA12, encoded in the leader to ORF61, also significantly increased the levels of VLT transcripts. Conversely, overexpression of VZVsncRNA13 using adeno-associated virus consistently increased VZV spread and progeny titers. These results suggest that sncRNA antisense to VZV may regulate VZV growth, possibly by affecting VLT expression. Transfection of LNAA to VZVsncRNA14 and VZVsncRNA9 decreased and increased VZV growth, respectively, while LNAA to three other VZVsncRNA had no significant effects on replication. These data strongly support the conclusion that VZV replication is modulated by multiple virally encoded sncRNA, revealing an additional layer of complexity of VZV regulation of lytic infections. This may inform the development of novel anti-sncRNA-based therapies for treatment of VZV diseases.IMPORTANCE Varicella-zoster virus (VZV) causes herpes zoster, a major health issue in the aging and immunocompromised populations. Small noncoding RNAs (sncRNA) are recognized as important actors in modulating gene expression. This study extends our previous work and shows that four VZVsncRNA clustering in and near ORF61 and antisense to the latency-associated transcript of VZV can positively influence productive VZV infection. The ability of multiple exogenous small oligonucleotides targeting VZVsncRNA to inhibit VZV replication strengthens the possibility that they may inform development of novel treatments for painful herpes zoster.

  • Varicella-Zoster Virus Expresses Multiple Small Noncoding RNAs.
    Journal of virology, 2017
    Co-Authors: Amos Markus, Paul R. Kinchington, Linoy Golani, Nishant Kumar Ojha, Tatiana Borodiansky-shteinberg, Ronald S. Goldstein
    Abstract:

    Many Herpesviruses express small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), that may play roles in regulating lytic and latent infections. None have yet been reported in varicella-zoster virus (VZV; also known as Human Herpesvirus 3 [HHV-3]). Here we analyzed next-generation sequencing (NGS) data for small RNAs in VZV-infected fibroblasts and Human embryonic stem cell-derived (hESC) neurons. Two independent bioinformatics analyses identified more than 20 VZV-encoded 20- to 24-nucleotide RNAs, some of which are predicted to have stem-loop precursors potentially representing miRNAs. These sequences are perfectly conserved between viruses from three clades of VZV. One NGS-identified sequence common to both bioinformatics analyses mapped to the repeat regions of the VZV genome, upstream of the predicted promoter of the immediate early gene open reading frame 63 (ORF63). This miRNA candidate was detected in each of 3 independent biological repetitions of NGS of RNA from fibroblasts and neurons productively infected with VZV using TaqMan quantitative PCR (qPCR). Importantly, transfected synthetic RNA oligonucleotides antagonistic to the miRNA candidate significantly enhanced VZV plaque growth rates. The presence of 6 additional small noncoding RNAs was also verified by TaqMan qPCR in productively infected fibroblasts and ARPE19 cells. Our results show VZV, like other Human Herpesviruses, encodes several sncRNAs and miRNAs, and some may regulate infection of host cells.IMPORTANCE Varicella-zoster virus is an important Human pathogen, with herpes zoster being a major health issue in the aging and immunocompromised populations. Small noncoding RNAs (sncRNAs) are recognized as important actors in modulating gene expression, and this study demonstrates the first reported VZV-encoded sncRNAs. Many are clustered to a small genomic region, as seen in other Human Herpesviruses. At least one VZV sncRNA was expressed in productive infection of neurons and fibroblasts that is likely to reduce viral replication. Since sncRNAs have been suggested to be potential targets for antiviral therapies, identification of these molecules in VZV may provide a new direction for development of treatments for painful herpes zoster.

R L Gilbert - One of the best experts on this subject based on the ideXlab platform.

  • Molecular biology of varicella-zoster virus. A review prepared for the UK Advisory Group on Chickenpox.
    The Journal of infection, 1998
    Co-Authors: D R Harper, R L Gilbert, D J Jeffries
    Abstract:

    Varicella-zoster virus (Human Herpesvirus 3; VZV) is one of eight herpes viruses that routinely infect Humans. It is classified as a member of the genus Varicellovirus, subfamily Alphaherpesvirinae, family Herpesviridae. Of the other Human herpes viruses it is most closely related to the herpes simplex viruses (also members of the Alphalerpesvirinae). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar membrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.

  • Molecular Biology of Varicella-zoster Virus: A review prepared for the UK Advisory Group on Chickenpox
    Journal of Infection, 1998
    Co-Authors: D R Harper, R L Gilbert, D J Jeffries
    Abstract:

    Varicella-zoster virus (Human Herpesvirus 3; VZVI is one of eight viruses that routinely infect Humans. It is classified as a member of the genus Varicellovirus , subfamily Alphaherpesvirinae , family Herpesviridae . Of the other Human herpes viruses it is ost closely related to the herpes simplex viruses (also members of the Alphaherpesvirinae ). Like all herpes viruses, the virus has a large double-stranded DNA genome within an icosahedral nucleocapsid. This is surrounded by a proteinaceous tegument and a trilaminar memhbrane derived from host-cell membranes into which the viral glycoproteins are inserted. The structure of the virion is summarized in Fig. 1.

  • Antiviral activity of 2-hydroxy fatty acids
    Antiviral Chemistry and Chemotherapy, 1996
    Co-Authors: David R. Harper, R L Gilbert, T. J. O'connor, D. Kinchington, N. Mahmood, R. A. J. Mcllhinney, D J Jeffries
    Abstract:

    Following an earlier demonstration of an antiviral effect against varicella-zoster virus (VZV, Human Herpesvirus 3) using 2-hydroxymyristic acid (2-hydroxy-tetradecanoic acid; 2-HM), an inhibitor of protein myristoylation, both 2-HM and 2-hydroxypalmitic acid (2-hydroxyhexadecanoic acid; 2-HP) have been tested against a range of viruses. Although both compounds inhibit the replication of varicella-zoster virus (VZV; Human Herpesvirus 3) they do not inhibit the replication of closely related Herpesviruses. They do, however, inhibit the replication of both poliovirus (a member of the Picornaviridae) and the Human immunodeficiency virus type 1 (HIV-1; a member of the Retroviridae). Neither compound is toxic to adherent cells by dye uptake assay, although limited toxicity is apparent to non-adherent cell lines at high concentrations. The mechanisms underlying these effects are discussed. A diminished effect of 2-hydroxymyristic acid when the compound is dissolved in dimethyl sulphoxide (DMSO) rather than ethanol is reported, and the implications for the use of DMSO as a 'universal solvent' for compound screening noted. Finally, it is suggested that targeting of 'virus-essential' cellular functions may provide an alternative route for inhibiting viral replication.

  • Effect of Inhibitors of Protein Myristoylation on Varicella-Zoster Virus Replication
    Antiviral Chemistry and Chemotherapy, 1994
    Co-Authors: R L Gilbert, D J Jeffries, David R. Harper, C. J. Blunt, R. A. J. Mcllhinney
    Abstract:

    Inhibitors of N-myristoyltransferase (NMT) have been shown to inhibit retrovirus replication, notably that of the Human immunodeficiency virus (HIV), where the absence of protein myristoylation inhibits viral replication. The authors have assayed 14 compounds derived from myristic acid for activity against varicella-zoster virus (Human Herpesvirus 3; VZV) by plaque reduction assay. Seven showed cytotoxicity and of the others, two failed to inhibit VZV replication. One of these was N-myristoylglycinaldiethylacetal (GoA), which has been reported to be active against HIV. 12-(methoxy) dodecanoic acid (13-oxamyristic acid), which has also been reported to inhibit HIV replication, was found to inhibit VZV replication but was cytotoxic at high concentrations. The greatest inhibitory effect without apparent toxicity was induced by 2-hydroxytetradecanoic acid and its enantiomers. The results of these assays provide further evidence that inhibitors of NMT have potential as antiviral agents against the many viruses...