UNIMAR

Philipps University Marburg

We study the structure-activity relationships of the receptor-binding sites (RBS) of influenza A viruses from humans and from different animal species by using synthetic and natural sialylglycoconjugates and solid-phase binding assays. These studies aim at the description of the receptor-binding specificity of influenza viruses in terms of molecular interactions between the HA and cellular receptors.
We are interested in the mechanisms by which HA and NA contribute to biological properties of influenza viruses such as host range, tissue tropism, pathogenicity, and immunogenicity. In particular, we try to specify the minimal changes in the HA and NA of influenza viruses of wild aquatic birds that are required for their successful transfer to other animal species and to humans.
In a collaboration with Dr. Nikolai Bovin´s lab, we design synthetic sialic acid-containing macromolecules, which would serve as decoy receptors and interfere with the virus attachment to host cells. This approach aims at the development of new anti-influenza drugs.
A balance between HA and NA activities with respect to sialylglycoconjugate receptors of specific host is required for efficient virus replication. We study what happens when this balance is disturbed by a reassortment event, virus transmission to a new host species, mutation in the HA or NA, etc. We use this knowledge to assess mechanisms by which virus could escape neutralization by NA inhibitors and to develop assays for monitoring virus resistance to this new class of anti-influenza drugs.

Five recent relevant publications:

1. M.Matrosovich, N.Zhou, Y.Kawaoka, and R.Webster. (1999). The surface glycoproteins of H5 influenza viruses isolated from humans, chickens, and wild aquatic birds have distinguishable properties. J. Virol. 73:1146-1155.
2. M.Matrosovich, A.Tuzikov, N.Bovin, A.Gambaryan, A.Klimov, M.R.Castrucci, I.Donatelli, and Y.Kawaoka. (2000). Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals.  J. Virol. 74:8502-8512.
3. M.N.Matrosovich, T.Y.Matrosovich, T.Gray, N.A.Roberts, and H.-D.Klenk. (2004). Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proc. Natl. Acad. Sci. U. S. A. 101:4620-4624.
4. M.N.Matrosovich, T.Y.Matrosovich, T.Gray, N.A.Roberts, and H.-D.Klenk. (2004). Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium. J. Virol. 78:12665-12667.
5. M.N.Matrosovich, H.-D.Klenk and Y.Kawaoka. (2006). Receptor specificity, host range and pathogenicity of influenza viruses In: “Influenza Virology: Current Topics”, Y.Kawaoka (Ed.), Caister Academic Press, p. 95-138.

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