Analysis Of The Interaction Of Measles Virus Envelope Glycoproteins With Its Receptors And Their Functional Sites During The Interaction

Measles virus Hemagglutinin protein (H) is the key molecule mediating MV infection in host cells. CD46 is the first identified MV receptor which specifically interacts with H protein. SLAM (signaling lymphocytic activation molecule) is a newly identified MV receptor. Based on our previous results, we study on the interactions of F, H and SLAM and further a mechanism of MV infection about three proteins trimer is also suggested.For measles viruses, fusion on the cell membrane is an important initial step in the entry into the infected cells. The recent research indicated that hemagglutinin firstly leads the conformational changes in the F protein then co-mediates the membrane fusion. In the work, we use the co-immunoprecipitation and pull-down assays to identify the interactions among fusion protein, hemagglutinin and SLAM, which reveal that the three proteins can form a functional complex to mediate the SLAM-dependent fusion. Moreover, under the confocal microscope, F and H proteincan show the cocapping mediated by the SLAM. So fusion protein not only is involved in the fusion but also might directly interact with the SLAM to be a new fusion-trimer model, which might account for the infection mechanism of measles virus.Our previous results have revealed that amino acid 429-438 in H protein is functionally involved in receptor binding and may constitute part of the receptor-binding determinants on H protein. Based on two mutants: pcDNA-Hml (429 Ser to 429 Ala) and pcDNA-Hm2 (436 Thr, 437 His to 436 Ala, 437 Ala)., which are generated by Dr. Chunling Hu, a further study on the fuctional sites between H and SLAM have been processed through Flow Cytometry and cell fusion assay. Moreover, the tH protein is used to screen a 15-mer phage display peptide library in this study. After 4 rounds of screening and sequence analysis, the deduced amino acid sequence of screened peptides MSKNIHFVVTLGWSL showed highly homologous with amino acid 56-70 of SLAM (MNKSIHIVVTMAKSL) .