Journal Article

Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells

Sosnovtsev, Stanislav V., Freeth, Jim, Jones, Ronald W., Tin, Christine M., Green, Kim Y., Sandoval-Jaime, Carlos, Smith, Alvin W., Soden, Jo, Parra, Gabriel I., Barnes, Donna

2017

Overview

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. IMPORTANCE Vesiviruses, 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. Vesiviruses, 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.

• Publisher: American Society for Microbiology
• Subject: Animals / Antibodies / Cats / Cell Adhesion Molecules - deficiency / Cell Adhesion Molecules - genetics / Cell Adhesion Molecules - isolation & purification / Cell Adhesion Molecules - metabolism / Cell culture / Cell lines / Cell Membrane - chemistry / Cell Membrane - genetics / Cell surface / CHO Cells / Cricetinae / Cricetulus / CRISPR / Genomes / Humans / Infections / Membrane proteins / Monoclonal antibodies / Propagation / Proteins / Receptors, Cell Surface - deficiency / Receptors, Cell Surface - genetics / Receptors, Cell Surface - isolation & purification / Receptors, Cell Surface - metabolism / Receptors, Virus - isolation & purification / Receptors, Virus - metabolism / Replication / Vesivirus - growth & development / Vesivirus - physiology / Virus Replication / Virus-like particles / Viruses