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Journal of virology2005; 79(13); 8431-8439; doi: 10.1128/JVI.79.13.8431-8439.2005

Attenuation of equine influenza viruses through truncations of the NS1 protein.

Abstract: Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, we found that in the case of equine influenza virus, the length of the NS1 protein did not correlate with the level of attenuation of that virus. With equine influenza virus, the mutant virus with the shortest NS1 protein turned out to be the least attenuated. We speculate that the basis for attenuation of the equine NS1 mutant viruses generated is related to their level of NS1 protein expression. Our findings show that the recombinant mutant viruses are impaired in their ability to inhibit IFN production in vitro and they do not replicate as efficiently as the parental recombinant strain in embryonated hen eggs, in MDCK cells, or in vivo in a mouse model. Therefore, these attenuated mutant NS1 viruses may have potential as candidates for a live equine influenza vaccine.
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Publication Date: 2005-06-16 PubMed ID: 15956587PubMed Central: PMC1143746DOI: 10.1128/JVI.79.13.8431-8439.2005Google Scholar: Lookup
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  • 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 presents the establishment of a reverse genetics system for the equine influenza virus, using this system to create three mutant viruses. The findings shift prior understanding about the NS1 protein’s role in equine influenza, suggesting that the length of the protein doesn’t correspond with virus attenuation. The mutants produced show promise for future live vaccines.

Creation of the Reverse Genetics System and Mutant Viruses

  • The major focus of the study was to establish a plasmid-based reverse genetics system for the equine influenza virus. A reverse genetics system is an advanced mechanism through which researchers can manipulate the genome of a virus and observe the resulting effects.
  • Utilizing this system, the researchers managed to generate three mutant viruses. These mutated versions encoded carboxy-terminally truncated NS1 proteins, meaning that the NS1 proteins created were shorter than those found in the natural virus.

Insights into the Role of NS1 Protein

  • The researchers tested the effects of varying the length of the NS1 protein. Previous research in human influenza had found that a virus lacking the NS1 gene could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 gene had a role in inhibiting this replication.
  • However, the study’s results with equine influenza virus demonstrated that the length of the NS1 protein didn’t correlate with the level of attenuation, or weakening, of the virus which contradicted earlier assumptions.
  • Moreover, a shorter NS1 protein led to the least attenuation, suggesting that the NS1 protein’s size isn’t necessarily an indicator of the virus’ virulence.
  • Therefore, they hypothesized that the attenuation of equine NS1 mutant viruses is more related to their level of NS1 protein expression rather than their length.

Potential Implications for Live Equine Influenza Vaccine

  • The study concludes that the newly created mutant viruses are impaired in their ability to inhibit IFN production in vitro. They also found that these mutants can’t replicate as efficiently as the parental recombinant strain in various mediums like embryonated hen eggs, MDCK cells, or in a mouse model.
  • Due to these characteristics, the research considers the attenuated mutant NS1 viruses potential candidates for creating a live equine influenza vaccine. As they are weakened and less able to inhibit IFN, they could possibly stimulate an immune response without causing the disease, which forms the basis for a possible live vaccine.

Cite This Article

APA
Quinlivan M, Zamarin D, García-Sastre A, Cullinane A, Chambers T, Palese P. (2005). Attenuation of equine influenza viruses through truncations of the NS1 protein. J Virol, 79(13), 8431-8439. https://doi.org/10.1128/JVI.79.13.8431-8439.2005

Publication

Journal of virology
ISSN: 0022-538X
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 79
Issue: 13
Pages: 8431-8439

Researcher Affiliations

Quinlivan, Michelle
  • Department of Microbiology, Box 1124, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, New York 10029, USA.
Zamarin, Dmitriy
    García-Sastre, Adolfo
      Cullinane, Ann
        Chambers, Thomas
          Palese, Peter

            MeSH Terms

            • Animals
            • Cell Line
            • Dogs
            • Horses
            • Influenza A virus / genetics
            • Influenza A virus / physiology
            • Kidney
            • Polymerase Chain Reaction
            • Recombination, Genetic
            • Sequence Deletion
            • Viral Nonstructural Proteins / genetics

            Grant Funding

            • P42 ES007384 / NIEHS NIH HHS
            • T32 AI007647 / NIAID NIH HHS
            • AI007647 / NIAID NIH HHS
            • P42ES007384 / NIEHS NIH HHS

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