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N-Linked Glycan at Residue 523 of Human Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase Masks a Second Receptor-Binding Site. (J Virol., abstract, RA-1004)
J Virol. 2010 Jan 6. [Epub ahead of print]
N-Linked Glycan at Residue 523 of Human Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase Masks a Second Receptor-Binding Site.
Mishin VP, Watanabe M, Taylor G, Devincenzo J, Bose M, Portner A, Alymova IV. - Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA; Center for Biomolecular Science, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, Scotland; Department of Pediatrics and Molecular Sciences, University of Tennessee, Le Bonheur Children's Medical Center, Memphis, TN 38103, USA; Pediatric Infectious Diseases, Children's Hospital of Wisconsin, Medical College of WI, Milwaukee, WI 52201, USA.
The hemagglutinin-neuraminidase (HN) glycoprotein plays a critical role in parainfluenza virus replication. We recently found that, in addition to the catalytic-binding site, the 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 the 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. Virology 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 the 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 hPIV-1, the N-linked glycan shields a second receptor-binding site on hPIV-3 HN.
PMID: 20053750 [PubMed - as supplied by publisher]
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J Virol. 2010 Jan 6. [Epub ahead of print]
N-Linked Glycan at Residue 523 of Human Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase Masks a Second Receptor-Binding Site.
Mishin VP, Watanabe M, Taylor G, Devincenzo J, Bose M, Portner A, Alymova IV. - Department of Infectious Diseases, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA; Center for Biomolecular Science, University of St. Andrews, North Haugh, St. Andrews, Fife KY16 9ST, Scotland; Department of Pediatrics and Molecular Sciences, University of Tennessee, Le Bonheur Children's Medical Center, Memphis, TN 38103, USA; Pediatric Infectious Diseases, Children's Hospital of Wisconsin, Medical College of WI, Milwaukee, WI 52201, USA.
The hemagglutinin-neuraminidase (HN) glycoprotein plays a critical role in parainfluenza virus replication. We recently found that, in addition to the catalytic-binding site, the 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 the 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. Virology 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 the 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 hPIV-1, the N-linked glycan shields a second receptor-binding site on hPIV-3 HN.
PMID: 20053750 [PubMed - as supplied by publisher]
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