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Related Concept Videos

Herpes01:28

Herpes

Herpes simplex type 1 (HSV‑1) is a widespread pathogen responsible for orolabial lesions. It is an enveloped, double-stranded DNA (dsDNA) virus belonging to the family Herpesviridae. Once the virus infects a host cell, its double‑stranded DNA genome is delivered into the nucleus, where a coordinated cascade of immediate‑early, early, and late gene expression directs viral DNA replication, structural protein synthesis, and virion assembly. After primary infection of epithelial cells, HSV-1...
Antiviral Nucleoside Inhibitors01:22

Antiviral Nucleoside Inhibitors

Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
Single-Strand DNA Binding Proteins01:03

Single-Strand DNA Binding Proteins

For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...

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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
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Short hairpin-loop-structured oligodeoxynucleotides reduce HSV-1 replication.

Alexander Falkenhagen1, Jochen Heinrich, Karin Moelling

  • 1University of Zurich, Gloriastrasse 30/32, CH-8006 Zurich, Switzerland. alex.falkenhagen@gmail.com

Virology Journal
|April 29, 2009
PubMed
Summary

Partially double-stranded oligodeoxynucleotides (ODNs) show promise for treating Herpes simplex virus (HSV) infections. These novel nucleic acid agents effectively inhibit HSV-1 replication, offering a potential alternative to existing antiviral therapies.

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Purification of Viral DNA for the Identification of Associated Viral and Cellular Proteins
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siRNA Electroporation to Modulate Autophagy in Herpes Simplex Virus Type 1-Infected Monocyte-Derived Dendritic Cells
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Purification of Viral DNA for the Identification of Associated Viral and Cellular Proteins
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Purification of Viral DNA for the Identification of Associated Viral and Cellular Proteins

Published on: August 31, 2017

Area of Science:

  • Virology
  • Molecular Biology
  • Antimicrobial Therapeutics

Background:

  • Herpes simplex virus (HSV) is a prevalent infectious agent with variable symptom severity, posing risks particularly to immunocompromised individuals.
  • Aciclovir, a common HSV treatment, faces increasing resistance, necessitating the development of alternative antiviral strategies.
  • Emerging nucleic acid-based therapies like antisense oligodeoxynucleotides (as) and small interfering ribonucleic acids (siRNAs) are being explored for antiviral applications.

Purpose of the Study:

  • To evaluate the antiviral potential of partially double-stranded hairpin loop-structured oligodeoxynucleotides (ODNs) against Herpes simplex virus type 1 (HSV-1) replication.
  • To assess the efficacy of novel ODNs designed against specific HSV-1 genes, including early and leaky late gene targets.
  • To compare the performance of these ODNs with existing siRNA-based treatments and investigate their application methods.

Main Methods:

  • Five partially double-stranded ODNs targeting HSV-1 mRNA sequences were designed based on active siRNAs.
  • Human lung fibroblasts (MRC-5) and monkey kidney cells (Vero) were transfected with ODNs before HSV-1 infection.
  • Viral replication was quantified using quantitative PCR and plaque assays to determine ODN efficacy.

Main Results:

  • All five tested ODNs demonstrated inhibitory effects on HSV-1 replication in both cell types.
  • Two ODNs exhibited statistically significant inhibition in both MRC-5 and Vero cells.
  • One ODN showed superior efficacy compared to a previously reported siRNA targeting the same HSV-1 UL5 gene mRNA.

Conclusions:

  • Partially double-stranded hairpin loop-structured ODNs represent a promising class of antiviral agents against HSV-1.
  • The observed antiviral activity is sequence-specific and dose-dependent, highlighting the targeted nature of ODN action.
  • ODNs can be effectively delivered, even without transfection reagents, suggesting potential for simplified therapeutic applications.