Identification of amino acid residues involved in the interaction between peste-des-petits-ruminants virus haemagglutinin protein and cellular receptors

Abstract

Peste-des-petits-ruminants virus (PPRV) haemagglutinin (H) protein mediates binding to cellular receptors and then initiates virus entry. To identify the key residues of PPRV H (Hv) protein of the Nigeria 75/1 strain involved in binding to receptors, interaction of the Hv and mutated Hv (mHv) proteins with receptors (SLAM and Nectin 4) and their mutants (mSLAM1, mSLAM2, mSLAM3 and mNectin 4) was investigated using surface plasmon resonance imaging (SPRi) and coimmunoprecipitation (co-IP) assays. The results showed that the Hv protein failed to interact with mSLAM3, but interacted at a strong or medium intensity with SLAM, mSLAM2, Nectin 4 and mNectin 4, and at a low level with mSLAM1. The mHv protein was unable to interact with SLAM and its mutants, but bound to Nectin 4 and mNectin 4 with medium and weak intensity, respectively. Further analysis showed that the Hv protein could precipitate mSLAM1, mSLAM2 and mNectin 4, but not mSLAM3. The mHv protein failed to coprecipitate with SLAM and its mutants. The binding activities of mNectin 4 and Nectin 4 to mHv were less than 30.36 and 51.94 % of the wild-type levels, respectively. Based on the results obtained, amino acids at positions R389, L464, I498, R503, R533, Y541, Y543, F552 and Y553 of H protein and I61, H62, L64, K76, K78, E123, H130, I210, A211, S226 and R227 in SLAM were identified to be essential for the specificity of H–SLAM interaction, while the critical residues of H–Nectin 4 interaction require further study. These findings would improve our understanding of the invasive mechanisms of PPRV.

Molecular epidemiology of peste des petits ruminants virus emergence in critically endangered Mongolian saiga antelope and other wild ungulates

“…The crystal structure of measles virus (MeV) H protein in complex with marmoset SLAM has been solved ( Hashiguchi et al, 2011 ) and shows that the receptor-binding domain (RBD) comprises four sites on MeV H which interact with SLAM and which are well conserved in PPRV H ( Abdullah et al, 2018 ). Several recent mutagenesis studies have also identified amino acid residues in PPRV H important for its ability to bind SLAM ( Meng et al, 2020 ) and induce cell fusion ( Gallo et al, 2021 ). In addition to cell entry, PPRV evidently requires efficient replicative and immune-evasive abilities for successful infection of atypical hosts, but the role of other viral genes in host range remains obscure.…”

Extracellular vesicles derived from PPRV-infected cells enhance signaling lymphocyte activation molecular (SLAM) receptor expression and facilitate virus infection

“…PPRV H protein is responsible for regulating viral adsorption and entry, determining pathogenicity, and generating protective antibodies during PPRV infection [ 7 , 59 , 64 , 67 , 68 ]. Our recently study has revealed that PPRV H can stimulates SLAM expression in goat PBMCs via suppressing miR-218 expression, a novel negative miRNA directly targeting SLAM gene [ 16 ].…”

Molecular epidemiology of peste des petits ruminants virus emergence in critically endangered Mongolian saiga antelope and other wild ungulates

“…The crystal structure of measles virus (MeV) H protein in complex with marmoset SLAM has been solved [28] and shows that the receptor binding domain (RBD) comprises four sites on MeV H which interact with SLAM and which are well conserved in PPRV H [24]. Several recent mutagenesis studies have also identified amino acid residues in PPRV H important for its ability to bind SLAM [29] and induce cell fusion [30]. In addition to cell entry, PPRV evidently requires efficient replicative and immune-evasive abilities for successful infection of atypical hosts, but the role of other viral genes in host range remains obscure.…”