Molecular Microbiology & Immunology

Irene Schulze , Ph.D. Professor Emeritus Molecular Microbiology & Immunology Saint Louis University School of Medicine Education: Ph.D., Saint Louis University, 1962 Email:schulzeit@slu.edu

Irene Schulze , Ph.D.

Research Summary:

The viruses which cause influenza are highly similar in structure but diverse in host range, virulence, and antigenic properties. Understanding the strategies by which these viruses continue to produce pandemic disease is largely dependent on our ability to determine how this functional diversity contributes to the ability of the virus to survive in the human population as well as in other mammalian and avian hosts. Two aspects of virus structure are involved. The virus has a segmented RNA genome which is synthesized by a virus-encoded polymerase that lacks the proof-reading capabilities needed for high fidelity genome replication. Uncloned populations of this virus therefore consist of particles with sequence diversity at both the nucleotide and protein level. Secondly, the virus contains surface glycoproteins whose structures are determined by the amino acid sequence encoded in the viral genome and by the oligosaccharide processing pathway of the host cell in which the virus is grown. Cell-specific glycosylation of the viral hemagglutinin (HA) can, therefore, enhance the biological diversity already present as a consequence of low fidelity genome replication. We are interested in determining the role of HA sequence diversity in determining the ability of these viruses to grow in cells of avian and mammalian origin. Our approaches include (1) determining the structural characteristics of Has on virions recovered directly from human and avian sources, and (2) characterizing a collection of HA variants each of which differs from the others by a single amino acid. In the latter approach we use both naturally occurring mutants and mutants made-to-order by site specific mutagenesis. The receptor binding properties of these HA variants, determined using well characterized neoglycolipids and/or neoglycoproteins, are then related to their ability to grow in cultured cells from different species. Using these approaches we can identify the structural properties of the HA which determine its conformational stability, its ability to interact with specific sialylated glycans, and its ability to infect cells from different animal species. Since the ability of antibodies to neutralize this virus is determined in part by the affinity of the HA for host cell receptors,we expect this information to help us design better diagnostic tests and vaccines. We also expect it to provide clues forpreventing the transfer of influenza viruses to and from natural reservoirs inlower animals.

Publications

Schulze, I.T., Aytay, S., Rajakumar, A., A. Renee Stewart, and Manger, I.D. (1993)
Hemagglutinin polymorphism and influenza virus host range. In Virus Strategies, Vol. 1,
(Doerfler, and Bohm, eds.) 260-271, Verlag-Chemie, Weinheim, Germany (1993).

Inkster, M.D., Hinshaw, V.S., and Schulze, I.T. (1993). The hemagglutinins of duck and
human H1 influenza viruses differ in sequence conservation and in glycosylation. J.
Virology 67(12):7436-7443.

Mir-Shekari, Y., Ashford, D.A., Harvey, D.J, Dwek, R.A., and Schulze, I.T. (1997).
Glycosylation of the hemagglutinin of influenze virus by mammalian cells - a site specific
study of glycan structures. J. Biol. Chem. 272: . Abstracts:

Inkster, M., Hinshaw, V., and Schulze, I.T. (1993). Characterization of the hemagglutinin
gene of an H1N1 influenza Avirus obtained directly from the gastrointestinal tract of a
duck. 12thAnnual Meeting of American Society for Virology, Davis, California,Abstract
#23-7 p.A53.

Inkster, M., Hinshaw, V., Rajakumar, A., and Schulze, I.T.(1993). The role of host cells in
determining the properties of avian and human influenza A (H1N1) virus hemagglutinins.
IX International Congress of Virology, Glasgow, (poster presentation).

Mir-Shekari, S.Y., Ashford, D.D., and Schulze, I.T. (1993). Glycosylation of the influenza
virus hemagglutinin. IX International Congress of Virology, Glasgow (oral presentation).

Mir-Shekari, S.Y., Ashford, D.A., and Schulze, I.T. (1993). Site-specific glycosylation of
the influenza virus hemagglutinin. XII International Symposium of Glycoconjugates,
Krakow, Poland, (poster presentation also selected for oral presentation).

Inkster, M.D., Ryerse J.S., and Schulze, I.T. (1994). Changes in the nucleoprotein and
the infectivity of duck influenza A(H1N1) virus populations during growth in Madin Darby canine kidney cells.
13th Meeting of the American Soc. for Virology, Madison, Wisconsin (p. 127)

Schulze, I.T., Platt., F., Inkster, M., Liang, Y., Mir-Shekari, Y., and Suber, A., (1994). Host
cell glycosylation pathways and influenza virus host range. Frontiers of Viral
Pathogenesis, Ninth International Conf. on Negative Strand Viruses (p. 50)