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Home / Equine Research Bank / Viruses / Inhibition of Venezuelan Equine Encephalitis Virus Using Sma...
Viruses2022; 14(8); 1628; doi: 10.3390/v14081628

Inhibition of Venezuelan Equine Encephalitis Virus Using Small Interfering RNAs.

Abstract: Acutely infectious new world alphaviruses such as Venezuelan Equine Encephalitis Virus (VEEV) pose important challenges to the human population due to a lack of effective therapeutic intervention strategies. Small interfering RNAs that can selectively target the viral genome (vsiRNAs) has been observed to offer survival advantages in several in vitro and in vivo models of acute virus infections, including alphaviruses such as Chikungunya virus and filoviruses such as Ebola virus. In this study, novel vsiRNAs that targeted conserved regions in the nonstructural and structural genes of the VEEV genome were designed and evaluated for antiviral activity in mammalian cells in the context of VEEV infection. The data demonstrate that vsiRNAs were able to effectively decrease the infectious virus titer at earlier time points post infection in the context of the attenuated TC-83 strain and the virulent Trinidad Donkey strain, while the inhibition was overcome at later time points. Depletion of Argonaute 2 protein (Ago2), the catalytic component of the RISC complex, negated the inhibitory effect of the vsiRNAs, underscoring the involvement of the siRNA pathway in the inhibition process. Depletion of the RNAi pathway proteins Dicer, MOV10, TRBP2 and Matrin 3 decreased viral load in infected cells, alluding to an impact of the RNAi pathway in the establishment of a productive infection. Additional studies focused on rational combinations of effective vsiRNAs and delivery strategies to confer better in vivo bioavailability and distribution to key target tissues such as the brain can provide effective solutions to treat encephalitic diseases resulting from alphavirus infections.
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Publication Date: 2022-07-26 PubMed ID: 35893693PubMed Central: PMC9331859DOI: 10.3390/v14081628Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

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 focuses on developing a therapeutic strategy for Venezuelan Equine Encephalitis Virus (VEEV) infection using small interfering RNAs, showing their effectiveness in reducing the virulence of the virus in the earlier stages after infection.

Research Purpose and Methodology

  • The study aimed to design a therapeutic strategy for VEEV, a new world alphavirus that poses significant health challenges due to the lack of treatment interventions. The researchers focused on small interfering RNAs (vsiRNAs) that target the viral genome directly.
  • These vsiRNAs were designed to target conserved regions in both the nonstructural and structural genes of the VEEV genome. The selection of these target sites was based on their potential for disrupting viral replication.
  • The vsiRNAs’ antiviral activity was evaluated on mammalian cells infected with VEEV, either with older, less virulent strains such as TC-83, or a more virulent strain – the Trinidad Donkey strain.

Findings and Implications

  • The study showed that vsiRNAs significantly decreased the VEEV’s infectious titer during the earlier stages post-infection. However, the inhibitory effect waned at later time points.
  • Depletion of a protein known as Argonaute 2 (Ago2), a key part of the RNA interference complex, removed the inhibitory effect of the vsiRNAs. This finding emphasizes the siRNA pathway’s role in the inhibition process against VEEV.
  • Reducing the quantities of RNAi pathway proteins Dicer, MOV10, TRBP2 and Matrin 3 also led to lower viral loads in VEEV-infected cells. This result hints at the RNAi pathway’s potential importance in preventing a full-blown VEEV infection.
  • The research suggests that more work is needed to optimize vsiRNAs and the methods by which they are delivered in the body for better tissue-targeting strategies. Particularly, these future studies could focus on ensuring that the vsiRNAs reach key viral target tissues, such as the brain, to effectively treat encephalitic diseases that result from alphavirus infections.

Cite This Article

APA
Haikerwal A, Barrera MD, Bhalla N, Zhou W, Boghdeh N, Anderson C, Alem F, Narayanan A. (2022). Inhibition of Venezuelan Equine Encephalitis Virus Using Small Interfering RNAs. Viruses, 14(8), 1628. https://doi.org/10.3390/v14081628

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 14
Issue: 8
PII: 1628

Researcher Affiliations

Haikerwal, Amrita
  • Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA.
Barrera, Michael D
  • Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA.
Bhalla, Nishank
  • Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA.
Zhou, Weidong
  • Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA 20110, USA.
Boghdeh, Niloufar
  • Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA.
Anderson, Carol
  • Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA.
Alem, Farhang
  • Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA.
Narayanan, Aarthi
  • Center for Infectious Disease Research, George Mason University, Manassas, VA 20110, USA.

MeSH Terms

  • Animals
  • Cell Line
  • Encephalitis Virus, Venezuelan Equine / physiology
  • Horses
  • Humans
  • RNA Helicases
  • RNA, Small Interfering / pharmacology
  • Virus Replication

Conflict of Interest Statement

The authors declare no conflict of interest.

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