Junction adhesion molecule is a receptor for reovirus.
Virus attachment to cells plays an essential role in viral tropism and disease. Reovirus serotypes 1 and 3 differ in the capacity to target distinct cell types in the murine nervous system and in the efficiency to induce apoptosis. The binding of viral attachment protein sigma1 to unidentified receptors controls these phenotypes. We used expression cloning to identify junction adhesion molecule (JAM), an integral tight junction protein, as a reovirus receptor. JAM binds directly to sigma1 and permits reovirus infection of nonpermissive cells. Ligation of JAM is required for reovirus-induced activation of NF-kappaB and apoptosis. Thus, reovirus interaction with cell-surface receptors is a critical determinant of both cell-type specific tropism and virus-induced intracellular signaling events that culminate in cell death.
Department of Microbiology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
E S
ES
Barton
J C
JC
Forrest
J L
JL
Connolly
J D
JD
Chappell
Y
Y
Liu
F J
FJ
Schnell
A
A
Nusrat
C A
CA
Parkos
T S
TS
Dermody
D000818:Animals; D017209:Apoptosis; D019556:COS Cells; D018938:Caco-2 Cells; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000502:physiology*; D016923:Cell Death; D002642:Chick Embryo; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D062726:Junctional Adhesion Molecules; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012087:Reoviridae / Q000737:chemistry*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D062726:Junctional Adhesion Molecules; D016328:NF-kappa B; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha