Neuraminidase-deficient Sendai virus HN mutants provide protection from homologous superinfection.
Binding of hemagglutinin-neuraminidase proteins (HN) to sialylated receptors initiates the infection process of several paramyxoviruses, whereas later in the viral life cycle, the neuramindase (NA) activity of newly synthesized HN destroys all receptors. Prior to NA action, expressed HN has to bind the receptor. To evaluate this HN-receptor complex with respect to receptor inactivation, three temperature-sensitive Sendai virus HN mutants carrying amino acid exchanges at positions 262, 264 and/or 461 were created that uncoupled NA activity from receptor binding at 39 degrees Celsius. Interestingly, at elevated temperature, when there is no detectable neuramindase activity, all infected cells are protected against homologous superinfection. Mutated HN protein on the cell surface is mainly bound to sialylated cell-surface components but can be released by treatment with NA. Thus, continuous binding to HN already inactivates the receptors quantitatively. Furthermore, mutant HN bound to receptors is prevented from being incorporated into virus particles in the absence of NA. It is shown here for the first time that during paramyxoviral infection, quantitative receptor inactivation already occurs due to binding of receptors to expressed HN protein without involvement of NA and is independent of NA activity of viral progeny. NA subsequently functions in the release of HN from the complex, coupled with desialysation of receptors. These findings could have implications for further antiviral drug development.
A Baumann
Christine
C
Department of Molecular Virology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152, Martinsried, Germany.
J Neubert
Wolfgang
W
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D015707:HN Protein / Q000235:genetics* / Q000378:metabolism; D008253:Macaca mulatta; D020125:Mutation, Missense; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D010253:Respirovirus Infections / Q000276:immunology / Q000517:prevention & control*; D029082:Sendai virus / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D015707:HN Protein; D011991:Receptors, Virus; D014613:Vaccines, Attenuated; D014765:Viral Vaccines