SLAM (CDw150) is a cellular receptor for measles virus

Abstract

Measles virus continues to be a major killer of children, claiming roughly one million lives a year. Measles virus infection causes profound immunosuppression, which makes measles patients susceptible to secondary infections accounting for high morbidity and mortality. The Edmonston strain of measles virus, and vaccine strains derived from it, use as a cellular receptor human CD46 (refs 3, 4), which is expressed on all nucleated cells; however, most clinical isolates of measles virus cannot use CD46 as a receptor. Here we show that human SLAM (signalling lymphocyte-activation molecule; also known as CDw150), a recently discovered membrane glycoprotein expressed on some T and B cells, is a cellular receptor for measles virus, including the Edmonston strain. Transfection with a human SLAM complementary DNA enables non-susceptible cell lines to bind measles virus, support measles virus replication and develop cytopathic effects. The distribution of SLAM on various cell lines is consistent with their susceptibility to clinical isolates of measles virus. The identification of SLAM as a receptor for measles virus opens the way to a better understanding of the pathogenesis of measles virus infection, especially the immunosuppression induced by measles virus.

The Nectin-4/Afadin Protein Complex and Intercellular Membrane Pores Contribute to Rapid Spread of Measles Virus in Primary Human Airway Epithelia

“…The reemergence of measles in insufficiently vaccinated populations in Europe and North America (2) reminds us that MV is extremely contagious, but the mechanisms favoring its spread remain incompletely understood. Once inhaled, MV bypasses the respiratory epithelium by infecting alveolar macrophages or dendritic cells that express the immune cell-specific protein signaling lymphocyte activation molecule (SLAM) (3)(4)(5). After extensive replication in SLAM-expressing cells in lymphatic organs, epithelial invasion occurs from the basolateral side (6); the virus is likely delivered by circulating SLAM-expressing immune cells (7,8) to epithelial cells expressing the adherens junction (AJ) protein nectin-4 (9,10).…”

Canine Distemper Virus Envelope Protein Interactions Modulated by Hydrophobic Residues in the Fusion Protein Globular Head

“…In the first step, the H protein binds to cell surface receptors (SLAM or nectin-4, depending on the type of target cells) through its membrane-distal cuboidal head domain (6)(7)(8)(9)(10). It is thought that receptor engagement then leads to opening of the central section of the H stalk through putative H head movements (11)(12)(13), which in turn actively destabilize prefusion F complexes (14,15).…”

Autophagy enhances the replication of Peste des petits ruminants virus and inhibits caspase-dependent apoptosis in vitro

“…In addition, MeV induces autophagy through the CD46-Cyt-1/GOPC pathway, which indicates that a cell surface pathogen receptor can directly trigger autophagy, a critical step for controlling infection [41,64]. Recent reports also demonstrate that SLAM recruits the vps34/Beclin-1 autophagic complex, suggesting that morbilliviruses might induce autophagy pathways upon receptor binding with the H protein [65]. Importantly, nectin-4 was identified as the epithelial receptor for several strains of MeV and PPRV [45,66].…”