Junctional adhesion molecule-A is required for hematogenous dissemination of reovirus.
Diverse families of viruses bind immunoglobulin superfamily (IgSF) proteins located in tight junctions (TJs) and adherens junctions of epithelium and endothelium. However, little is known about the roles of these receptors in the pathogenesis of viral disease. Junctional adhesion molecule-A (JAM-A) is an IgSF protein that localizes to TJs and serves as a receptor for mammalian reovirus. We inoculated wild-type (WT) and isogenic JAM-A(-/-) mice perorally with reovirus and found that JAM-A is dispensable for viral replication in the intestine but required for systemic dissemination. Reovirus replication in the brain and tropism for discrete neural regions are equivalent in WT and JAM-A(-/-) mice following intracranial inoculation, suggesting a function for JAM-A in reovirus spread to extraintestinal sites. JAM-A promotes reovirus infection of endothelial cells, providing a conduit for the virus into the bloodstream. These findings indicate that a broadly expressed IgSF viral receptor specifically mediates hematogenous dissemination in the host.
Antar
Annukka A R
AA
Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Konopka
Jennifer L
JL
Campbell
Jacquelyn A
JA
Henry
Rachel A
RA
Perdigoto
Ana L
AL
Carter
Bruce D
BD
Pozzi
Ambra
A
Abel
Ty W
TW
Dermody
Terence S
TS
D000818:Animals; D001835:Body Weight; D001921:Brain / Q000473:pathology / Q000821:virology; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000502:physiology*; D042783:Endothelial Cells / Q000821:virology; D006321:Heart / Q000821:virology; D007422:Intestines / Q000473:pathology / Q000821:virology; D008099:Liver / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000502:physiology*; D011991:Receptors, Virus / Q000172:deficiency / Q000502:physiology*; D012087:Reoviridae / Q000502:physiology*; D012088:Reoviridae Infections / Q000821:virology*; D016019:Survival Analysis; D014779:Virus Replication
D015815:Cell Adhesion Molecules; C498686:F11r protein, mouse; D011956:Receptors, Cell Surface; D011991:Receptors, Virus