Abstract:
In paramyxoviruses, the interactions between fusion protein (F) and hemagglutinin-neuraminidase (HN) are critical in determining the host range, virulence and spread of these viruses. To investigate the function of the fusion interaction region (FIR) in the mechanism of membrane fusion, Newcastle disease virus (NDV) and human parainfluenza virus type 3 (hPIV3) were selected as research objects. Site-directed and fragment replacement mutagenesis methods were used to obtain chimeras, then we identified two conserved amino acids, serine (S) and aspartic acid (D) in the FIR through comparison with highly similar sequences in NDV and hPIV3 HN, and mutated them into alanine respectively, namely NDV S51A, NDV D55A, hPIV3 S51A and hPIV3 D55A. Cell surface expression, as well as the activity of receptor binding, neuraminidase, fusion promotion and semi-fusion, was determined. There was no significant difference in cell surface expression or neuraminidase activity between each chimera, mutant and wild-type(P<0.05), but fusion promotion activity was reduced significantly (P<0.05): C1, C2, NDV S51A, NDV D55A, hPIV3 S51A, and hPIV3 D55A was 7%, 9%, 27%, 19%, 17% and 21% of the wild-type level, respectively. C1, C2, NDV S51A, NDV D55A, hPIV3 S51A and hPIV3 D55A also showed reductions in receptor binding activity, which was 14.7%, 22.3%, 35.5%, 28.8%, 33.9% and 40.2%, respectively. These data suggest that the FIR in the stalk domain plays a very important role in the fusion promotion activity and receptor binding activity of NDV and hPIV3. S51 and D55 are key amino acids in the FIR in the stalk domain.
Highlights:
Newcastle disease virus and human parainfluenza virus type 3 were selected as research objects. It is the first time to study the functions of the fusion interaction region in the stalk domain of hemagglutinin-neuraminidase.
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