Viruses and sialic acids
The first critical step during a viral infection is the binding to specific receptors at the surface of target cells. Several viruses use glycans, especially heparan sulfate or sialic acids as receptors or co-receptors. Due to the fact that sialic acids are ubiquitously present, influenza viruses will eventually bind also to sialic acids on cells which are not susceptible for infection. They may also bind to highly glycosylated mucins, which represent an unspecific antimicrobial barrier. To allow release from such “decoy”-receptors, several viruses acquired sialic acid modifying enzymes (neuraminidases or O-acetylesterases). These enzymes are also termed “receptor-destroying enzymes”.
We identified a number of economically important viruses interacting with O-acetylated sialic acids. Several viruses belonging to the families of the Orthomyxoviridae, Coronaviridae and Toroviridae possess acetylesterase activities capable of de-O-acetylating sialic acids. First, the sialate-9-O-acetylesterases of influenza C viruses and bovine coronavirus were identified, which specifically hydrolyze 5-N-acetyl-9-O-acetyl-neuraminic acid (Neu5,9Ac2).
More recently, we detected 4-O-acetylesterases in murine coronaviruses and in infectious salmon anemia virus. While the coronavirus esterases are specific for either Neu5,9Ac2 or Neu4,5Ac2, the esterases of toroviruses preferentially hydrolyze Neu5,9Ac2. Among the toroviral esterases, we detected a novel substrate specificity: Bovine toroviruses preferentially hydrolyze the double-O-acetylated sialic acid Neu5,7,(8),9Ac3.
In order to gain knowledge on the molecular basis of the different substrate specificities, we use different approaches:
- We have developed a reverse genetics system to specifically modify the genes of influenza C viruses. In the future, we want to determine the strucute and function of the viral esterase in more detail.
- We are developing antivirals, especially for human-pathogenic coronaviruses.
- Expression of recombinant viral esterases to determine the distribution and functions of O-acetylated sialic acids in normal and cancer tissues.