N-linked glycan at residue 523 of human parainfluenza virus type 3 hemagglutinin-neuraminidase masks a second receptor-binding site

Vasiliy P. Mishin, Makiko Watanabe, Garry Taylor, John Devincenzo, Michael Bose, Allen Portner, Irina V. Alymova

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The hemagglutinin-neuraminidase (HN) glycoprotein plays a critical role in parainfluenza virus replication. We recently found that in addition to the catalytic binding site, HN of human parainfluenza virus type 1 (hPIV-1) may have a second receptor-binding site covered by an N-linked glycan at residue 173, which is near the region of the second receptor-binding site identified in Newcastle disease virus (NDV) HN (I. A. Alymova, G. Taylor, V. P. Mishin, M. Watanabe, K. G. Murti, K. Boyd, P. Chand, Y. S. Babu, and A. Portner, J. Virol. 82:8400-8410, 2008). Sequence analysis and superposition of the NDV and hPIV-3 HN dimer structures revealed that, similar to what was seen in hPIV-1, the N-linked glycan at residue 523 on hPIV-3 HN may cover a second receptor-binding site. Removal of this N-linked glycosylation site by an Asn-to-Asp substitution at residue 523 (N523D) changed the spectrum of the mutant virus's receptor specificity, delayed its elution from both turkey and chicken red blood cells, reduced mutant sensitivity (by about half) to the selective HN inhibitor BCX 2855 in hemagglutination inhibition tests, and slowed its growth in LLC-MK2 cells. The neuraminidase activity of the mutant and its sensitivity to BCX 2855 in neuraminidase inhibition assays did not change, indicating that the mutation did not affect the virus's catalytic-binding site and that all observed effects were caused by the exposure of the purported second receptor-binding site. Our data are consistent with the idea that, similar to the case for hPIV-1, the N-linked glycan shields a second receptor-binding site on hPIV-3 HN.

Original languageEnglish (US)
Pages (from-to)3094-3100
Number of pages7
JournalJournal of Virology
Volume84
Issue number6
DOIs
StatePublished - Mar 1 2010

Fingerprint

Human parainfluenza virus 3
Human parainfluenza virus 1
sialidase
Hemagglutinins
Neuraminidase
hemagglutinins
Masks
Polysaccharides
binding sites
polysaccharides
Binding Sites
viruses
receptors
Newcastle disease virus
Catalytic Domain
mutants
HN Protein
Hemagglutination Inhibition Tests
Virus Receptors
Virus Attachment

All Science Journal Classification (ASJC) codes

  • Immunology
  • Virology

Cite this

N-linked glycan at residue 523 of human parainfluenza virus type 3 hemagglutinin-neuraminidase masks a second receptor-binding site. / Mishin, Vasiliy P.; Watanabe, Makiko; Taylor, Garry; Devincenzo, John; Bose, Michael; Portner, Allen; Alymova, Irina V.

In: Journal of Virology, Vol. 84, No. 6, 01.03.2010, p. 3094-3100.

Research output: Contribution to journalArticle

Mishin, Vasiliy P. ; Watanabe, Makiko ; Taylor, Garry ; Devincenzo, John ; Bose, Michael ; Portner, Allen ; Alymova, Irina V. / N-linked glycan at residue 523 of human parainfluenza virus type 3 hemagglutinin-neuraminidase masks a second receptor-binding site. In: Journal of Virology. 2010 ; Vol. 84, No. 6. pp. 3094-3100.
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AU - Taylor, Garry

AU - Devincenzo, John

AU - Bose, Michael

AU - Portner, Allen

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