title: S-acylation of influenza virus proteins: Are enzymes for fatty acid attachment promising drug targets?
abstract: Covalent attachment of saturated fatty acids (palmitate and stearate) to hemagglutinin (HA) of influenza virus is a protein modification essential for viral replication. The enzymes catalysing acylation of viral proteins have not been identified, but likely candidates that acylate cellular substrates are members of a protein family that contain a DHHC (Asp-His-His-Cys) cysteine-rich domain. Since 23 DHHC-proteins with distinct, only partly overlapping substrate specificities are present in humans, only a few of them might acylate HA in airway cells of the lung. We argue here that these DHHC-proteins might be promising drug targets since their blockade should result in suppression of viral replication, while acylation of cellular proteins will not be (or very little) compromised.
authors.affiliation: Institute of Virology, Veterinary Medicine, Free University Berlin, Robert von Ostertag-Str. 7-13, Building 35, 14163 Berlin, Germany. Electronic address: mveit@zedat.fu-berlin.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Veit
authors.affiliation: Institute of Virology, Veterinary Medicine, Free University Berlin, Robert von Ostertag-Str. 7-13, Building 35, 14163 Berlin, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Siche
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000737:chemistry*; D000818:Animals; D004285:Dogs; D005227:Fatty Acids / Q000737:chemistry*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006801:Humans; D054878:Lipoylation; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D009975:Orthomyxoviridae / Q000502:physiology*; D019308:Palmitic Acid / Q000737:chemistry; D013229:Stearic Acids / Q000737:chemistry; D019065:Virus Assembly; D014779:Virus Replication
chemical_list: D005227:Fatty Acids; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D013229:Stearic Acids; D019308:Palmitic Acid; C031183:stearic acid; D000217:Acyltransferases
keywords: DHHC-protein; Drug target; HA; Influenza virus; M2; Palmitoylation