YEARS

2011-2013

AUTHORS

Elena I Frolova

TITLE

Multiple functions of VEEV nsP3 in virus replication

ABSTRACT

The Old World and the New World alphaviruses represent two groups of geographically isolated viruses, which independently evolved for almost 3,000 years. Accordingly, they accumulated strong differences in the nonstructural and structural genes and cause different diseases in vertebrate hosts. The New World alphaviruses, which include Venezuelan (VEEV), eastern and western equine encephalitis viruses, are continuously circulating in the Central, South and North Americas and have the ability to cause encephalitis with frequent fatal outcomes in humans and horses. We have recently demonstrated that the Old World and the New World alphaviruses differ not only in the severity of the disease, but also in the molecular mechanisms of virus-host interactions, particularly by interfering with the cellular antiviral response. Thus, our knowledge about replication of the less pathogenic, Old World alphaviruses cannot be directly applied to the encephalitogenic New World viruses, as they have accumulated strong differences in their replication mechanisms. In the preliminary studies, we found that the nonstructural nsP3 proteins of geographically isolated viruses, VEEV and Sindbis, form distinct intracellular complexes and interact with different host factors. We have also found that the carboxy terminal fragment of VEEV nsP3 is critical for virus replication. nsP3 is the least studied viral protein, and it s functions in the viral life cycle have not yet been defined. No information about VEEV nsP3 in particular is available to date. In this project, we will perform extensive characterization of the structures and functions of different VEEV nsP3-containing complexes, and define the roles of the hypervariable fragment and nsP3 phosphorylation in viral replication. Understanding the role of VEEV nsP3 in virus replication will lead to development of new therapeutic means and the next generation of vaccines against highly pathogenic alphaviruses.

FUNDED PUBLICATIONS

  • Early events in alphavirus replication determine the outcome of infection.
  • Hypervariable domain of nonstructural protein nsP3 of Venezuelan equine encephalitis virus determines cell-specific mode of virus replication.
  • Hypervariable domains of nsP3 proteins of New World and Old World alphaviruses mediate formation of distinct, virus-specific protein complexes.
  • How to use: Click on a object to move its position. Double click to open its homepage. Right click to preview its contents.

    Download the RDF metadata as:   json-ld nt turtle xml License info


    20 TRIPLES      17 PREDICATES      21 URIs      9 LITERALS

    Subject Predicate Object
    1 grants:85a3ad129ff2a4cfd94de9f008ea3eba sg:abstract The Old World and the New World alphaviruses represent two groups of geographically isolated viruses, which independently evolved for almost 3,000 years. Accordingly, they accumulated strong differences in the nonstructural and structural genes and cause different diseases in vertebrate hosts. The New World alphaviruses, which include Venezuelan (VEEV), eastern and western equine encephalitis viruses, are continuously circulating in the Central, South and North Americas and have the ability to cause encephalitis with frequent fatal outcomes in humans and horses. We have recently demonstrated that the Old World and the New World alphaviruses differ not only in the severity of the disease, but also in the molecular mechanisms of virus-host interactions, particularly by interfering with the cellular antiviral response. Thus, our knowledge about replication of the less pathogenic, Old World alphaviruses cannot be directly applied to the encephalitogenic New World viruses, as they have accumulated strong differences in their replication mechanisms. In the preliminary studies, we found that the nonstructural nsP3 proteins of geographically isolated viruses, VEEV and Sindbis, form distinct intracellular complexes and interact with different host factors. We have also found that the carboxy terminal fragment of VEEV nsP3 is critical for virus replication. nsP3 is the least studied viral protein, and it s functions in the viral life cycle have not yet been defined. No information about VEEV nsP3 in particular is available to date. In this project, we will perform extensive characterization of the structures and functions of different VEEV nsP3-containing complexes, and define the roles of the hypervariable fragment and nsP3 phosphorylation in viral replication. Understanding the role of VEEV nsP3 in virus replication will lead to development of new therapeutic means and the next generation of vaccines against highly pathogenic alphaviruses.
    2 sg:endYear 2013
    3 sg:fundingAmount 366250.0
    4 sg:fundingCurrency USD
    5 sg:hasContribution contributions:ac71af5a363431189e35279d713f58c4
    6 sg:hasFieldOfResearchCode anzsrc-for:11
    7 anzsrc-for:1108
    8 sg:hasFundedPublication articles:281d16b31e54eb166da92367ace3ddd2
    9 articles:c042c1e3f43d085dbc5ea59aad8b1d18
    10 articles:e773ed76c44dc3b1a40687f40e1c7947
    11 sg:hasFundingOrganization grid-institutes:grid.419681.3
    12 sg:hasRecipientOrganization grid-institutes:grid.265892.2
    13 sg:language English
    14 sg:license http://scigraph.springernature.com/explorer/license/
    15 sg:scigraphId 85a3ad129ff2a4cfd94de9f008ea3eba
    16 sg:startYear 2011
    17 sg:title Multiple functions of VEEV nsP3 in virus replication
    18 sg:webpage http://projectreporter.nih.gov/project_info_description.cfm?aid=8293638
    19 rdf:type sg:Grant
    20 rdfs:label Grant: Multiple functions of VEEV nsP3 in virus replication
    HOW TO GET THIS DATA PROGRAMMATICALLY:

    JSON-LD is a popular JSON format for linked data.

    curl -H 'Accept: application/ld+json' 'http://scigraph.springernature.com/things/grants/85a3ad129ff2a4cfd94de9f008ea3eba'

    N-Triples is a line-based linked data format ideal for batch operations .

    curl -H 'Accept: application/n-triples' 'http://scigraph.springernature.com/things/grants/85a3ad129ff2a4cfd94de9f008ea3eba'

    Turtle is a human-readable linked data format.

    curl -H 'Accept: text/turtle' 'http://scigraph.springernature.com/things/grants/85a3ad129ff2a4cfd94de9f008ea3eba'

    RDF/XML is a standard XML format for linked data.

    curl -H 'Accept: application/rdf+xml' 'http://scigraph.springernature.com/things/grants/85a3ad129ff2a4cfd94de9f008ea3eba'






    Preview window. Press ESC to close (or click here)


    ...