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Journal of virology2008; 82(8); 4028-4041; doi: 10.1128/JVI.02330-07

Venezuelan equine encephalitis virus capsid protein inhibits nuclear import in Mammalian but not in mosquito cells.

Abstract: Venezuelan equine encephalitis virus (VEEV) represents a continuous public health threat in the United States. It has the ability to cause fatal disease in humans and in horses and other domestic animals. We recently demonstrated that replicating VEEV interferes with cellular transcription and uses this phenomenon as a means of downregulating a cellular antiviral response. VEEV capsid protein was found to play a critical role in this process, and its approximately 35-amino-acid-long peptide, fused with green fluorescent protein, functioned as efficiently as did the entire capsid. We detected a significant fraction of VEEV capsid associated with nuclear envelope, which suggested that this protein might regulate nucleocytoplasmic trafficking. In this study, we demonstrate that VEEV capsid and its N-terminal sequence efficiently inhibit multiple receptor-mediated nuclear import pathways but have no effect on the passive diffusion of small proteins. The capsid protein of the Old World alphavirus Sindbis virus and the VEEV capsid, with a previously defined frameshift mutation, were found to have no detectable effect on nuclear import. Importantly, the VEEV capsid did not noticeably interfere with nuclear import in mosquito cells, and this might play a critical role in the ability of the virus to develop a persistent, life-long infection in mosquito vectors. These findings demonstrate a new aspect of VEEV-host cell interactions, and the results of this study are likely applicable to other New World alphaviruses, such as eastern and western equine encephalitis viruses.
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Publication Date: 2008-02-06 PubMed ID: 18256144PubMed Central: PMC2293000DOI: 10.1128/JVI.02330-07Google Scholar: Lookup
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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.

This research article investigates how the Venezuelan equine encephalitis virus (VEEV) capsid protein inhibits nuclear import in mammalian cells but does not affect mosquito cells, suggesting its potential role in the virus’s ability to cause persistent, lifelong infections in mosquito vectors.

Overview of Research

  • This research focuses on the Venezuelan equine encephalitis virus (VEEV), which poses a significant public health threat as it can cause fatal diseases in humans and various domestic animals such as horses.
  • Researchers previously discovered that the VEEV interferes with cellular transcription and uses this mechanism to downregulate the cellular antiviral response, with the VEEV capsid protein playing a critical role in this process.
  • In the current study, a significant portion of the VEEV capsid was found associating with the nuclear envelope, indicating that this protein might be involved in regulating nucleocytoplasmic trafficking— the movement of molecules between the nucleus and cytoplasm of the cells.

Research Findings

  • The study shows that the VEEV capsid and its N-terminal sequence effectively inhibit multiple receptor-mediated nuclear import pathways—mechanisms by which molecules are transported into the cell nucleus. However, they do not impact the passive diffusion of small proteins, a process where individual molecules move from an area of high concentration to one of low concentration.
  • In comparison, the capsid protein of the Sindbis virus—an Old World alphavirus—and VEEV capsid’s previously identified frameshift mutation, had no detectable effect on the nuclear import process.

Significance of Findings

  • Significantly, the VEEV capsid does not appear to interfere with nuclear import in mosquito cells, which researchers suggest may be a critical factor in the virus’s ability to establish persistent, lifelong infections in mosquito vectors.
  • This discovery sheds new light on the interactions between VEEV and host cells, furthering the understanding of how New World alphaviruses, such as the VEEV and equine encephalitis viruses, manipulate cellular functions to facilitate their replication and persistent infections in their vector organisms.

Cite This Article

APA
Atasheva S, Garmashova N, Frolov I, Frolova E. (2008). Venezuelan equine encephalitis virus capsid protein inhibits nuclear import in Mammalian but not in mosquito cells. J Virol, 82(8), 4028-4041. https://doi.org/10.1128/JVI.02330-07

Publication

Journal of virology
ISSN: 1098-5514
NlmUniqueID: 0113724
Country: United States
Language: English
Volume: 82
Issue: 8
Pages: 4028-4041

Researcher Affiliations

Atasheva, Svetlana
  • Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-1072, USA.
Garmashova, Natalia
    Frolov, Ilya
      Frolova, Elena

        MeSH Terms

        • Active Transport, Cell Nucleus
        • Animals
        • Capsid Proteins / genetics
        • Capsid Proteins / metabolism
        • Cell Line
        • Cell Nucleus / metabolism
        • Cricetinae
        • Culicidae
        • Encephalitis Virus, Venezuelan Equine / physiology
        • Frameshift Mutation
        • Humans
        • Mammals
        • Mice
        • Mutant Proteins / metabolism
        • Nucleocytoplasmic Transport Proteins / antagonists & inhibitors
        • Sindbis Virus / physiology

        Grant Funding

        • U54 AI057156 / NIAID NIH HHS
        • R21 AI050537 / NIAID NIH HHS
        • AI050537 / NIAID NIH HHS
        • R01 AI050537-05 / NIAID NIH HHS
        • R01 AI050537 / NIAID NIH HHS

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