Epithelial-mesenchymal transition abolishes the susceptibility of polarized epithelial cell lines to measles virus.
Measles virus (MV), an enveloped negative-strand RNA virus, remains a major cause of morbidity and mortality in developing countries. MV predominantly infects immune cells by using signaling lymphocyte activation molecule (SLAM; also called CD150) as a receptor, but it also infects polarized epithelial cells, forming tight junctions in a SLAM-independent manner. Although the ability of MV to infect polarized epithelial cells is thought to be important for its transmission, the epithelial cell receptor for MV has not been identified. A transcriptional repressor, Snail, induces epithelial-mesenchymal transition (EMT), in which epithelial cells lose epithelial cell phenotypes, such as adherens and tight junctions. In this study, EMT was induced by expressing Snail in a lung adenocarcinoma cell line, II-18, which is highly susceptible to wild-type MV. Snail-expressing II-18 cells lost adherens and tight junctions. Microarray analysis confirmed the induction of EMT in II-18 cells and suggested a novel function of Snail in protein degradation and distribution. Importantly, wild-type MV no longer entered EMT-induced II-18 cells, suggesting that the epithelial cell receptor is down-regulated by the induction of EMT. Other polarized cell lines, NCI-H358 and HT-29, also lost susceptibility to wild-type MV when EMT was induced. However, the complete formation of tight junctions rather reduced MV entry into HT-29 cells. Taken together, these data suggest that the unidentified epithelial cell receptor for MV is involved in the formation of epithelial intercellular junctions.
Shirogane
Yuta
Y
Department of Virology, Faculty of Medicine, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. yuuta@virology.med.kyushu-u.ac.jp
Takeda
Makoto
M
Tahara
Maino
M
Ikegame
Satoshi
S
Nakamura
Takanori
T
Yanagi
Yusuke
Y
D000818:Animals; D002460:Cell Line; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology / Q000821:virology; D005434:Flow Cytometry; D020022:Genetic Predisposition to Disease; D005822:Genetic Vectors; D016679:Genome, Viral; D006801:Humans; D008213:Lymphocyte Activation; D008253:Macaca mulatta / Q000821:virology; D008457:Measles / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission / Q000662:veterinary; D008459:Measles virus / Q000235:genetics / Q000472:pathogenicity*; D051916:Membrane Cofactor Protein / Q000502:physiology; D008648:Mesoderm / Q000166:cytology* / Q000502:physiology / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids; D011991:Receptors, Virus / Q000502:physiology; D019108:Tight Junctions / Q000502:physiology; D017201:Virus Shedding
D051916:Membrane Cofactor Protein; D011991:Receptors, Virus