S-acylation of influenza virus proteins: Are enzymes for fatty acid attachment promising drug targets?

Vaccine. 2015 Dec 8;33(49):7002-7. doi: 10.1016/j.vaccine.2015.08.095. Epub 2015 Sep 19.

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.

Keywords: DHHC-protein; Drug target; HA; Influenza virus; M2; Palmitoylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Acyltransferases / chemistry*
  • Animals
  • Dogs
  • Fatty Acids / chemistry*
  • Hemagglutinin Glycoproteins, Influenza Virus / chemistry*
  • Humans
  • Lipoylation
  • Madin Darby Canine Kidney Cells
  • Mice
  • Orthomyxoviridae / physiology*
  • Palmitic Acid / chemistry
  • Stearic Acids / chemistry
  • Virus Assembly
  • Virus Replication

Substances

  • Fatty Acids
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Stearic Acids
  • Palmitic Acid
  • stearic acid
  • Acyltransferases