Molecular Evolution and Characterization of Hemagglutinin (H) in Peste des Petits Ruminants Virus.

Abstract

Peste des Petits Ruminants (PPR) is an acute, highly contagious, and febrile viral disease that affects both domestic and wild small ruminants. The disease has become a major obstacle to the development of sustainable Agriculture. Hemagglutinin (H), the envelope glycoprotein of Peste des Petits Ruminants Virus (PPRV), plays a crucial role in regulating viral adsorption and entry, thus determining pathogenicity, and release of newly produced viral particles. In order to accurately understand the epidemic of the disease and the interactions between the virus and host, we launch the work. Here, we examined H gene from all four lineages of the PPRV to investigate evolutionary and epidemiologic dynamics of PPRV by the Bayesian method. In addition, we predicted positive selection sites due to selective pressures. Finally, we studied the interaction between H protein and SLAM receptor based on homology model of the complex. Phylogenetic analysis suggested that H gene can also be used to investigate evolutionary and epidemiologic dynamics of PPRV. Positive selection analysis identified four positive selection sites in H gene, in which only one common site (aa246) was detected by two methods, suggesting strong operation structural and/or functional constraint of changes on the H protein. This target site may be of interest for future mutagenesis studies. The results of homology modeling showed PPRVHv-shSLAM binding interface and MVH-maSLAM binding interface were consistent, wherein the groove in the B4 blade and B5 of the head domain of PPRVHv bound to the AGFCC' β-sheets of the membrane-distal ectodomain of shSLAM. The binding regions could provide insight on the nature of the protein for epitope vaccine design, novel drug discovery, and rational drug design against PPRV.