Evidence that maturation of the N-linked glycans of the respiratory syncytial virus (RSV) glycoproteins is required for virus-mediated cell fusion: The effect of alpha-mannosidase inhibitors on RSV infectivity.
Glycan heterogeneity of the respiratory syncytial virus (RSV) fusion (F) protein was demonstrated by proteomics. The effect of maturation of the virus glycoproteins-associated glycans on virus infectivity was therefore examined using the alpha-mannosidase inhibitors deoxymannojirimycin (DMJ) and swainsonine (SW). In the presence of SW the N-linked glycans on the F protein appeared in a partially mature form, whereas in the presence of DMJ no maturation of the glycans was observed. Neither inhibitor had a significant effect on G protein processing or on the formation of progeny virus. Although the level of infectious virus and syncytia formation was not significantly affected by SW-treatment, DMJ-treatment correlated with a one hundred-fold reduction in virus infectivity. Our data suggest that glycan maturation of the RSV glycoproteins, in particular those on the F protein, is an important step in virus maturation and is required for virus infectivity.
McDonald
Terence P
TP
MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, UK.
Jeffree
Chris E
CE
Li
Ping
P
Rixon
Helen W McL
HW
Brown
Gaie
G
Aitken
James D
JD
MacLellan
Kirsty
K
Sugrue
Richard J
RJ
D002459:Cell Fusion; D045744:Cell Line, Tumor; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D006026:Glycoside Hydrolases; D006801:Humans; D008855:Microscopy, Electron, Scanning; D011134:Polysaccharides / Q000378:metabolism*; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D043323:alpha-Mannosidase / Q000037:antagonists & inhibitors*
D004791:Enzyme Inhibitors; D006023:Glycoproteins; D011134:Polysaccharides; D014764:Viral Proteins; D006026:Glycoside Hydrolases; D043323:alpha-Mannosidase