Effective treatment of respiratory alphaherpesvirus infection using RNA interference.
Abstract: Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA's), delivered intranasally, could prove a valuable alternative for infection control. siRNA's against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model. METHODOLOGY/PRINCIPAL FNDINGS: siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection. Conclusions: siRNA treatment has potential for both prevention and early treatment of EHV-1 infections.
Publication Date: 2009-01-05 PubMed ID: 19122813PubMed Central: PMC2606062DOI: 10.1371/journal.pone.0004118Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article focuses on the effective treatment of respiratory alphaherpesvirus infection using RNA interference. The study specifically uses Equine herpesvirus type 1 (EHV-1) and Small interfering RNAs (siRNA’s), evaluating their potential in decreasing the infection in a mouse model.
Objective and Problem Statement
- The main objective of the research was centered on exploring the potential of using small interfering RNAs (siRNA’s) for the treatment of Equine herpesvirus type 1 (EHV-1) infection.
- The issue stemmed from the fact that EHV-1, a variant of Alphaherpesvirinae, is a significant pathogen in horses, causing respiratory disease, neurological disorders, and abortions. In spite of vaccines available, they only offer partial protection and there are no efficient metaphylactic and therapeutic agents available.
Methodology
- The research examined siRNAs against two essential EHV-1 genes, which encode the viral helicase (Ori) and glycoprotein B.
- The potential of these siRNAs to decrease EHV-1 infection was evaluated in a mouse model.
- The siRNA’s were delivered intranasally to evaluate their efficacy in controlling the infection.
- The effectiveness of siRNA treatment in vitro (in the lab) and in vivo (in a living organism) were tested and measured in terms of virus production reduction and plaque size, and the reduction of viral replication and clinical signs respectively.
Findings
- The siRNA therapy in vitro significantly reduced virus production and plaque size. And when the siRNAs were used in combination, viral titers went down 80-fold.
- The research also discovered that siRNA therapy tested in vivo significantly brought down viral replication and clinical signs. Intranasal treatment did not need a transport vehicle and was effective when given up to 12 hours before or after infection.
Conclusion
- The research concluded that siRNA treatment holds potential for both prevention and early treatment of EHV-1 infections.
- The research is groundbreaking as it not only aims to make a significant breakthrough in the treatment of EHV-1 but also sets a platform for further research on the use of siRNA’s as an alternative treatment strategy for various infections.
Cite This Article
APA
Fulton A, Peters ST, Perkins GA, Jarosinski KW, Damiani A, Brosnahan M, Buckles EL, Osterrieder N, Van de Walle GR.
(2009).
Effective treatment of respiratory alphaherpesvirus infection using RNA interference.
PLoS One, 4(1), e4118.
https://doi.org/10.1371/journal.pone.0004118 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
MeSH Terms
- Administration, Intranasal
- Animals
- Anti-Inflammatory Agents / therapeutic use
- DNA-Binding Proteins / genetics
- Disease Models, Animal
- Herpesviridae Infections / therapy
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid / genetics
- Horse Diseases / therapy
- Horse Diseases / virology
- Horses
- Inflammation / drug therapy
- Mice
- Mice, Inbred BALB C
- RNA Interference / immunology
- RNA, Small Interfering / therapeutic use
- Respiratory Tract Infections / therapy
- Respiratory Tract Infections / veterinary
- Respiratory Tract Infections / virology
- Viral Envelope Proteins / genetics
- Viral Proteins / genetics
- Virus Replication
Conflict of Interest Statement
The authors have declared that no competing interests exist.
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