Bioinformatically-predicted varicella zoster virus small non-coding RNAs are expressed in lytically-infected epithelial cells and neurons

Linoy Golani-Zaidie; Tatiana Borodianskiy-Shteinberg; Punam Bisht; Biswajit Das; Paul R. Kinchington; Ronald S. Goldstein

doi:10.1016/j.virusres.2019.197773

Bioinformatically-predicted varicella zoster virus small non-coding RNAs are expressed in lytically-infected epithelial cells and neurons

Linoy Golani-Zaidie, Tatiana Borodianskiy-Shteinberg, Punam Bisht, Biswajit Das, Paul R. Kinchington, Ronald S. Goldstein

The Mina and Everard Goodman Faculty of Life Sciences

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Most herpesviruses use both host and viral small non-coding RNAs (sncRNA), especially microRNA, to modulate infection. Bioinformatic analyses of NGS data obtained from Varicella Zoster virus (VZV)-infected cells predicted 24 VZVsncRNA, seven of which were confirmed to be expressed in infected fibroblasts and neurons using stem-loop quantitative reverse transcription PCR (SL-PCR). We here assayed for the expression of all 24 of the bioinformatically predicted VZVsncRNA in cells productively infected by VZV using SL-PCR. 23 of the 24 predicted sequences were detected in VZV-infected ARPE19 cells and 19 of the 24 sequences in infected human neurons generated by two methods from embryonic stem cells. We also show that blocking one of two newly-tested VZV-encoded sncRNA using locked nucleotide antagonists significantly increased viral replication. These findings suggest that further study of VZV encoded sncRNA could elucidate an additional level of regulation of the life cycle of this pathogenic human herpesvirus.

Original language	English
Article number	197773
Journal	Virus Research
Volume	274
DOIs	https://doi.org/10.1016/j.virusres.2019.197773
State	Published - Dec 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier B.V.

Funding

This research was supported by NIH grant R01 AI122640 and US-Israel Binational Science Foundation 2017259 to RG and PRK. RG was also supported by Israel Science Foundation grant 254/16 . PRK acknowledges additional support from core grant EY08098, and unrestricted funds from Research to Prevent Blindness, Inc and The Eye & Ear foundation of Pittsburgh. Linoy Golani was supported in part by a President’s PhD fellowship from Bar-Ilan University. Thanks to Dr. Amos Markus for many helpful discussions and critical reading of the manuscript, and to Dr. Moran Topf for technical assistance. Monoclonal antibody was developed by Drs. M. McCutcheon and S. Carroll was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa. This research was supported by NIH grant R01 AI122640 and US-Israel Binational Science Foundation2017259 to RG and PRK. RG was also supported by Israel Science Foundation grant 254/16. PRK acknowledges additional support from core grant EY08098, and unrestricted funds from Research to Prevent Blindness, Inc and The Eye & Ear foundation of Pittsburgh. Linoy Golani was supported in part by a President's PhD fellowship from Bar-Ilan University. Thanks to Dr. Amos Markus for many helpful discussions and critical reading of the manuscript, and to Dr. Moran Topf for technical assistance. Monoclonal antibody was developed by Drs. M. McCutcheon and S. Carroll was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the NICHD and maintained by The University of Iowa.

Funders	Funder number
Research to Prevent Blindness, Inc and The Eye & Ear foundation of Pittsburgh
US-Israel Binational Science	Foundation2017259
US-Israel Binational Science Foundation	2017259
National Institutes of Health
National Institute of Allergy and Infectious Diseases	R01AI122640
Eye and Ear Foundation of Pittsburgh
Research to Prevent Blindness
University of Iowa
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Bar-Ilan University
Israel Science Foundation	254/16, EY08098

Keywords

Human neurons
Neurotropic virus
Non-coding RNA
Varicella zoster virus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.virusres.2019.197773

Cite this

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title = "Bioinformatically-predicted varicella zoster virus small non-coding RNAs are expressed in lytically-infected epithelial cells and neurons",

abstract = "Most herpesviruses use both host and viral small non-coding RNAs (sncRNA), especially microRNA, to modulate infection. Bioinformatic analyses of NGS data obtained from Varicella Zoster virus (VZV)-infected cells predicted 24 VZVsncRNA, seven of which were confirmed to be expressed in infected fibroblasts and neurons using stem-loop quantitative reverse transcription PCR (SL-PCR). We here assayed for the expression of all 24 of the bioinformatically predicted VZVsncRNA in cells productively infected by VZV using SL-PCR. 23 of the 24 predicted sequences were detected in VZV-infected ARPE19 cells and 19 of the 24 sequences in infected human neurons generated by two methods from embryonic stem cells. We also show that blocking one of two newly-tested VZV-encoded sncRNA using locked nucleotide antagonists significantly increased viral replication. These findings suggest that further study of VZV encoded sncRNA could elucidate an additional level of regulation of the life cycle of this pathogenic human herpesvirus.",

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author = "Linoy Golani-Zaidie and Tatiana Borodianskiy-Shteinberg and Punam Bisht and Biswajit Das and Kinchington, {Paul R.} and Goldstein, {Ronald S.}",

note = "Publisher Copyright: {\textcopyright} 2019 Elsevier B.V.",

year = "2019",

month = dec,

doi = "10.1016/j.virusres.2019.197773",

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AU - Das, Biswajit

AU - Kinchington, Paul R.

AU - Goldstein, Ronald S.

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AB - Most herpesviruses use both host and viral small non-coding RNAs (sncRNA), especially microRNA, to modulate infection. Bioinformatic analyses of NGS data obtained from Varicella Zoster virus (VZV)-infected cells predicted 24 VZVsncRNA, seven of which were confirmed to be expressed in infected fibroblasts and neurons using stem-loop quantitative reverse transcription PCR (SL-PCR). We here assayed for the expression of all 24 of the bioinformatically predicted VZVsncRNA in cells productively infected by VZV using SL-PCR. 23 of the 24 predicted sequences were detected in VZV-infected ARPE19 cells and 19 of the 24 sequences in infected human neurons generated by two methods from embryonic stem cells. We also show that blocking one of two newly-tested VZV-encoded sncRNA using locked nucleotide antagonists significantly increased viral replication. These findings suggest that further study of VZV encoded sncRNA could elucidate an additional level of regulation of the life cycle of this pathogenic human herpesvirus.

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Bioinformatically-predicted varicella zoster virus small non-coding RNAs are expressed in lytically-infected epithelial cells and neurons

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

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