The Interactions Between The Hemagglutinin Of Peste Des Petitis Ruminants Virus And Its Host Receptors

The epidemics of peste des petits ruminants (PPR) increase the poverty of undeveloped countriesand threaten animal health and food security heavily, thus was announced to be controlled anderadicated with global efforts by the Food and Agriculture Organization of the United Nations (FAO) in2012. However, the fundamental research on peste des petits ruminants virus (PPRV) is still backwardand the expansion of its distribution, particularly among wild animals greatly challenged the PPReradication project.The interactions between another morbilivirus-measles virus (MV) and its receptors play animportant role in virus infection. We are keen to figure out whether PPRV also use Nectin4to mediatethe shedding of offspring virions? If so, is it because PPRV vaccine strain cannot interact with Nectin4that it doesn’t ‘shed’ offsprings? Dose the hemaggluntinin (H) protein solely determine host specificity?We predicted the interactions between PPRV H wildtype (Hw)／vaccine (Hv) and sheep SLAM/Nectin4, analyzed their interaction mechanisms, determined the crucial domains and amino acids usingmolecular modeling, and finally acquired the following results by experiments:1. Plasmids containing Hw/Hv and sheep Nectin4locate in the cytoplasm of CHO,293T cells; Co-Ipshows both Hw and Hv have interactions with sheep Nectin4; sheep Nectin4mRNAs were expressedmainly in the epithelial tissues of digestive and respiratory tracts which is consistent with the tissuetropism of PPRV in sheep along with the mRNAs expressions of SLAM; transfection of sheep Nectin4can obviously increase the reproduction of PPRV cultured in Vero cell line. All the results aboveconfirm that Nectin4is the receptor for both PPRV wildtype strain and vaccine strain.2. The IgV domain of sheep Nectin4involves in the interaction with PPRV Hw.3. Both PPRV Hw and Hv possess the molecular basis to bind human SLAM, while the mutations ofSer550Trp，Arg191Tyr，Arg191Phe，Thr545Trp，Ser548Trp，Ser534Trp of Hw/Hv would increase theinteraction energies between Hw/Hv and human SLAM.To sum up, we have successfully identified PPRV’s receptor-Nectin4, and analyzed the interactionmodels and mechanisms between PPRH Hw/Hv and receptor SLAM/Nectin4respectively, whichprovide theoretical significance and valuable reference for future development of PPRV diagnosis andvaccines.