beta3 Integrins mediate the cellular entry of hantaviruses that cause respiratory failure.
Newly emerged hantaviruses replicate primarily in the pulmonary endothelium, cause acute platelet loss, and result in hantavirus pulmonary syndrome (HPS). We now report that specific integrins expressed on platelets and endothelial cells permit the cellular entry of HPS-associated hantaviruses. Infection with HPS-associated hantaviruses, NY-1 and Sin Nombre virus (SNV), is inhibited by antibodies to beta3 integrins and by the beta3-integrin ligand, vitronectin. In contrast, infection with the nonpathogenic (no associated human disease) Prospect Hill virus was inhibited by fibronectin and beta1-specific antibodies but not by beta3-specific antibodies or vitronectin. Transfection with recombinant alphaIIb beta3 or alphav beta3 integrins rendered cells permissive to NY-1 and SNV but not Prospect Hill virus infection, indicating that alphaIIb beta3 and alphav beta3 integrins mediate the entry of NY-1 and SNV hantaviruses. Furthermore, entry is divalent cation independent, not blocked by arginine-glycine-aspartic acid peptides and still mediated by, ligand-binding defective, alphaIIb beta3-integrin mutants. Hence, NY-1 and SNV entry is independent of beta3 integrin binding to physiologic ligands. These findings implicate integrins as cellular receptors for hantaviruses and indicate that hantavirus pathogenicity correlates with integrin usage.
Gavrilovskaya
I N
IN
The Department of Medicine, Stony Brook University, HSC T17, Room 60, Stony Brook, NY 11794, USA.
Shepley
M
M
Shaw
R
R
Ginsberg
M H
MH
Mackow
E R
ER
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000821:virology*; D006476:Orthohantavirus / Q000502:physiology*; D018778:Hantavirus Infections / Q000821:virology*; D018804:Hantavirus Pulmonary Syndrome / Q000821:virology*; D006801:Humans; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D014709:Vero Cells; D014779:Virus Replication / Q000502:physiology*
D015703:Antigens, CD; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins