title: Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells.
abstract: The Hom-1 vesivirus was reported in 1998 following the inadvertent transmission of the animal calicivirus San Miguel sea lion virus to a human host in a laboratory. We characterized the Hom-1 strain and investigated the mechanism by which human cells could be infected. An expression library of 3,559 human plasma membrane proteins was screened for reactivity with Hom-1 virus-like particles, and a single interacting protein, human junctional adhesion molecule 1 (hJAM1), was identified. Transient expression of hJAM1 conferred susceptibility to Hom-1 infection on nonpermissive Chinese hamster ovary (CHO) cells. Virus infection was markedly inhibited when CHO cells stably expressing hJAM were pretreated with anti-hJAM1 monoclonal antibodies. Cell lines of human origin were tested for growth of Hom-1, and efficient replication was observed in HepG2, HuH7, and SK-CO15 cells. The three cell lines (of hepatic or intestinal origin) were confirmed to express hJAM1 on their surface, and clustered regularly interspaced short palindromic repeats/Cas9-mediated knockout of the hJAM1 gene in each line abolished Hom-1 propagation. Taken together, our data indicate that entry of the Hom-1 vesivirus into these permissive human cell lines is mediated by the plasma membrane protein hJAM1 as a functional receptor.IMPORTANCEVesiviruses, such as San Miguel sea lion virus and feline calicivirus, are typically associated with infection in animal hosts. Following the accidental infection of a laboratory worker with San Miguel sea lion virus, a related virus was isolated in cell culture and named Hom-1. In this study, we found that Hom-1 could be propagated in a number of human cell lines, making it the first calicivirus to replicate efficiently in cultured human cells. Screening of a library of human cell surface membrane proteins showed that the virus could utilize human junctional adhesion molecule 1 as a receptor to enter cells and initiate replication. The Hom-1 virus presents a new system for the study of calicivirus biology and species specificity.
authors.affiliation: Caliciviruses Section, Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA ss216m@nih.gov.
authors.forename: Stanislav V
authors.initials: SV
authors.lastname: Sosnovtsev
authors.affiliation: Caliciviruses Section, Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sandoval-Jaime
authors.affiliation: Caliciviruses Section, Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Gabriel I
authors.initials: GI
authors.lastname: Parra
authors.affiliation: Caliciviruses Section, Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Tin
authors.affiliation: Caliciviruses Section, Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Jones
authors.affiliation: Retrogenix Ltd., Whaley Bridge, High Peak, United Kingdom.
authors.forename: Jo
authors.initials: J
authors.lastname: Soden
authors.affiliation: Retrogenix Ltd., Whaley Bridge, High Peak, United Kingdom.
authors.forename: Donna
authors.initials: D
authors.lastname: Barnes
authors.affiliation: Retrogenix Ltd., Whaley Bridge, High Peak, United Kingdom.
authors.forename: Jim
authors.initials: J
authors.lastname: Freeth
authors.affiliation: Laboratory for Calicivirus Studies, Oregon State University, Corvallis, Oregon, USA.
authors.forename: Alvin W
authors.initials: AW
authors.lastname: Smith
authors.affiliation: Caliciviruses Section, Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland, USA.
authors.forename: Kim Y
authors.initials: KY
authors.lastname: Green
mesh_terms: D000818:Animals; D016466:CHO Cells; D002415:Cats; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D011991:Receptors, Virus / Q000302:isolation & purification / Q000378:metabolism*; D029342:Vesivirus / Q000254:growth & development / Q000502:physiology*; D014779:Virus Replication
chemical_list: D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D011956:Receptors, Cell Surface; D011991:Receptors, Virus