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Natural resistance-associated macrophage protein is a cellular receptor for sindbis virus in both insect and

Patrick P Rose1, Sheri L Hanna, Anna Spiridigliozzi

  • 1Department of Microbiology, University of Pennsylvania, Philadelphia, USA.

Cell Host & Microbe
|August 17, 2011
PubMed

Insights

The natural resistance-associated macrophage protein (NRAMP) is essential for Sindbis virus entry into cells. This discovery identifies a new host factor for alphavirus infection, potentially revealing broader implications for mosquito-borne virus research.

Area of Science:

  • Virology
  • Cell Biology
  • Genetics

Background:

  • Alphaviruses are mosquito-borne viruses, with some causing emerging human diseases.
  • Host factors and receptors for alphavirus entry are largely unknown.
  • Sindbis virus is a key member of the Alphavirus genus.

Purpose of the Study:

  • To identify host cell surface molecules required for Sindbis virus binding and entry.
  • To investigate the role of natural resistance-associated macrophage protein (NRAMP) in alphavirus infection.
  • To determine if NRAMP homologs are involved in mammalian cell alphavirus entry.

Main Methods:

  • Utilized a Drosophila system to screen for host factors.
  • Generated and analyzed dNRAMP mutant flies.
  • Tested the role of the vertebrate homolog, NRAMP2, in mammalian cell infection.
  • Employed alphavirus glycoprotein chimeras to pinpoint the stage of entry.

Main Results:

  • Identified natural resistance-associated macrophage protein (NRAMP) as crucial for Sindbis virus binding and entry in Drosophila.
  • dNRAMP mutant flies showed protection against Sindbis virus infection.
  • Vertebrate NRAMP2 facilitated Sindbis virus binding and infection in mammalian cells.
  • Murine cells lacking NRAMP2 were resistant to Sindbis virus infection.
  • Glycoprotein chimera experiments confirmed NRAMP2's role in the viral entry process.

Conclusions:

  • NRAMP family proteins are essential host factors for Sindbis virus entry.
  • NRAMP2 acts as a receptor or entry mediator for Sindbis virus in mammalian cells.
  • Conserved multipass membrane proteins, like transporters, may be utilized by other alphaviruses for entry.

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