Roles of the highly conserved amino acids in the second receptor binding site of the Newcastle disease virus HN protein
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RESEARCH
Open Access
Roles of the highly conserved amino acids in the second receptor binding site of the Newcastle disease virus HN protein Yaqing Liu1, Miaomiao Chi1, Ying Liu1, Hongling Wen1, Li Zhao1, Yanyan Song1, Na Liu1 and Zhiyu Wang1,2*
Abstract Background: The paramyxovirus haemagglutinin-neuraminidase (HN) is a multifunctional protein that is responsible for attachment to receptors, removal of receptors from infected cells to prevent viral self-aggregation (neuraminidase, NA) and fusion promotion. It is commonly accepted that there are two receptor binding sites in the globular head of HN, and the second receptor binding site is only involved in the function of receptor binding and fusion promotion. Methods: 10 conserved residues in the second receptor binding site of Newcastle disease virus (NDV) HN were chosen and substituted to alanine (A). The desired mutants were examined to detect the functional change in hemadsorption (HAD) ability, NA activity and fusion promotion ability. Results: The HAD and fusion promotion ability of mutants C172A, R174A, C196A, D198A, Y526A and E547A were abolished. Compared with wild-type (wt) HN, the HAD of mutants T167A, S202A and R516A decreased to 55.81, 44.53, 69.02%, respectively, and the fusion promotion ability of these three mutants decreased to 54.74, 49.46, 65.26%, respectively; however, mutant G171A still maintained fusion promotion ability comparable with wt HN but had impaired HAD ability. All the site-directed mutations altered the NA activity of NDV HN without affecting protein cell surface expression. Conclusions: The data suggest that mutants C172A, R174A, C196A, D198A, Y526A and E547A do not allow the conformational change that is required for fusion promotion ability and HAD activity, while the other mutants only affect the conformational change to a limited extent, except mutant G171A with intact fusion promotion ability. Overall, the conserved amino acids in the second receptor binding site, especially residues C172, R174, C196, D198, Y526 and E547, are crucial to normal NDV HN protein function. Keywords: Newcastle disease virus, Haemagglutinin-neuraminidase, Receptor binding, Fusion promotion
Background The Paramyxoviridae family includes many pathogenic viruses covering both medical and veterinary areas, such as human parainfluenza viruses (hPIVs), Nipah virus (NiV), Sendai virus (SV), mumps virus (MuV) and Newcastle disease virus (NDV) [1–5]. NDV is usually used as an ideal model to study the pathogenic mechanism of paramyxoviruses. NDV, also named avian paramyxovirus type 1 (APMV-1), is an enveloped, non-segmented, * Correspondence: [email protected] 1 Department of Virology, School of Public Health, Shandong University, Jinan 250012, China 2 The Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University, Jinan 250012, China
single-stranded, negative-sense RNA virus whose genome encodes the nucleocapsid (NP) protein, phosphoprotein (P), matrix (M) protein, fusion (F) protein, haemagglutinin-neuraminidase (
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