Morbillivirus Receptors and Tropism: Multiple Pathways for Infection

Sato, Hiroki; Yoneda, Misako; Honda, Tomoyuki; Kai, Chieko

In 2011, two independent groups reported identification of the EpR. Both groups utilized microarray data from susceptible versus non-susceptible cell lines and compared the membrane protein gene transcripts. Noyce et al. (2011) described the susceptibility of many different tumor cell lines to MeV infection and selected susceptible and non-susceptible cell lines. They filtered the microarray data for membrane protein genes, and produced a short list of 11 candidate receptors. Of these, only human PVRL4 (nectin-4), a tumor cell marker found on breast, lung, and ovarian carcinomas, rendered cells susceptible to MeV infection. Transient knockdown of nectin-4 using siRNA abolished MeV infection in these cell lines. Furthermore, antibodies specific for human nectin-4 inhibited MeV infection. Mühlebach et al. (2011) performed microarray analysis of seven epithelial cell lines from human airways or bladder previously characterized as permissive (three lines) or non-permissive (four lines), and identified that nectin-4 renders CHO cells susceptible to MeV. It was demonstrated that the V domain of nectin-4 binds strongly to MeV-H (Mühlebach et al., 2011 ; Figure 4) .