title: Natural resistance-associated macrophage protein is a cellular receptor for sindbis virus in both insect and mammalian hosts.
abstract: Alphaviruses, including several emerging human pathogens, are a large family of mosquito-borne viruses with Sindbis virus being a prototypical member of the genus. The host factor requirements and receptors for entry of this class of viruses remain obscure. Using a Drosophila system, we identified the divalent metal ion transporter natural resistance-associated macrophage protein (NRAMP) as a host cell surface molecule required for Sindbis virus binding and entry into Drosophila cells. Consequently, flies mutant for dNRAMP were protected from virus infection. NRAMP2, the ubiquitously expressed vertebrate homolog, mediated binding and infection of Sindbis virus into mammalian cells, and murine cells deficient for NRAMP2 were nonpermissive to infection. Alphavirus glycoprotein chimeras demonstrated that the requirement for NRAMP2 is at the level of Sindbis virus entry. Given the conserved structure of alphavirus glycoproteins, and the widespread use of transporters for viral entry, other alphaviruses may use conserved multipass membrane proteins for infection.
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, USA.
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Rose
authors.forename: Sheri L
authors.initials: SL
authors.lastname: Hanna
authors.forename: Anna
authors.initials: A
authors.lastname: Spiridigliozzi
authors.forename: Nattha
authors.initials: N
authors.lastname: Wannissorn
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Beiting
authors.forename: Susan R
authors.initials: SR
authors.lastname: Ross
authors.forename: Richard W
authors.initials: RW
authors.lastname: Hardy
authors.forename: Shelly A
authors.initials: SA
authors.lastname: Bambina
authors.forename: Mark T
authors.initials: MT
authors.lastname: Heise
authors.forename: Sara
authors.initials: S
authors.lastname: Cherry
mesh_terms: D018354:Alphavirus Infections / Q000378:metabolism / Q000821:virology; D000818:Animals; D019921:Biotinylation / Q000379:methods; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D009033:Culicidae; D004330:Drosophila / Q000821:virology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D007501:Iron / Q000494:pharmacology; D008322:Mammals; D051379:Mice; D034622:RNA Interference; D020871:RNA Stability; D011991:Receptors, Virus / Q000378:metabolism*; D012845:Sindbis Virus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity*; D014162:Transfection; D018116:Vesiculovirus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D053585:Virus Attachment; D053586:Virus Internalization; D014902:West Nile virus / Q000187:drug effects / Q000235:genetics / Q000472:pathogenicity; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2
chemical_list: D027682:Cation Transport Proteins; D029721:Drosophila Proteins; D007501:Iron; D011991:Receptors, Virus; D000099173:Natural Resistance-associated Macrophage Protein 1; D000099236:Solute Carrier Family 11, Member 2