title: Gene silencing of β-galactosamide α-2,6-sialyltransferase 1 inhibits human influenza virus infection of airway epithelial cells.
abstract: BACKGROUND
  Human influenza virus hemagglutinin prefers to use sialic acid (SA) receptors via α-2,6 linkages. The β-galactoside α-2,6-sialyltransferase I (ST6Gal I) protein is encoded by the ST6GAL1 gene and is responsible for the addition of α-2,6 linked SA to the Galβ1-4GlcNAc disaccharide of glycans and glycoproteins found on the cellular surface. Therefore, ST6GAL1 could be a potential target for anti-influenza therapeutics. We used specific small interfering RNAs (siRNAs) to block expression of ST6GAL1 and limit distribution of SA receptors on the surface of airway epithelial cells.
  
  
  RESULTS
  The siRNA duplexes we used inhibited ST6GAL1 mRNA expression and subsequent expression of the encoding protein. As a result, synthesis of α-2,6 SA galactose was inhibited. Adsorption of influenza virus particles to the surface of cells transfected with appropriate specific siRNAs was significantly reduced. Intracellular viral genome copy number and virus titer within the supernatant of cells transfected with siRNAs was significantly reduced in a dose-dependent manner compared with those for untransfected cells and cells transfected with non-specific siRNAs.
  
  
  CONCLUSIONS
  We used siRNAs targeting ST6GAL1 to inhibit the expression of certain cell surface receptors, thereby preventing virus adsorption. This resulted in the inhibition of human influenza virus infection. Our findings are a significant development in the identification of potential new anti-influenza drug targets.
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.forename: Wenbo
authors.initials: W
authors.lastname: Huang
authors.forename: Yutao
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenda
authors.initials: W
authors.lastname: Guan
authors.forename: Runfeng
authors.initials: R
authors.lastname: Li
authors.affiliation: State Key Laboratory of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, 1st KangDa Road, Guangzhou, China. jeffyah@163.com.
authors.forename: Zifeng
authors.initials: Z
authors.lastname: Yang
authors.forename: Nanshan
authors.initials: N
authors.lastname: Zhong
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D002460:Cell Line; D004847:Epithelial Cells / Q000201:enzymology* / Q000821:virology*; D020868:Gene Silencing; D006801:Humans; D009975:Orthomyxoviridae / Q000502:physiology*; D034741:RNA, Small Interfering / Q000378:metabolism; D012799:Sialyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019562:Viral Load; D053586:Virus Internalization; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D015703:Antigens, CD; D034741:RNA, Small Interfering; D012799:Sialyltransferases; C093493:ST6GAL1 protein, human; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase