Date of Award

5-2010

Document Type

Thesis

Degree Name

Master of Science (MS)

Program

Biomedical Sciences

Track

Molecular Sciences

Research Advisor

Jonathan A. McCullers Ph.D.

Committee

Julia Hurwitz, Ph.D. Pat Ryan, Ph.D.

Keywords

glycosylation, hemagglutinin, influenza, neutralizing antibodies, T-cells

Abstract

Three separate influenza pandemics have emerged in the human population since 1918, each characterized by viruses that lack N-linked glycosylation sites on the globular head of the hemagglutinin protein. In contrast, recent non-pandemic isolates have acquired such sites. Here we constructed isogenic viruses containing differing numbers of additional N-linked glycosylation sites to assess the impact on the host immune response. These studies show that mice infected with a glycosylated virus remain susceptible to challenge with a non-glycosylated virus, glycosylated viruses elicit an inferior immune response, and in this context T-cell pathology and death may occur. We conclude from these data that glycosylation leads to a lack of neutralization coupled with a robust T-cell response. Specifically, glycosylation of HA seems to shield neutralizing antibody epitopes while leaving T-cell epitopes unaffected. These results may be particularly significant in the context of the recent influenza pandemic.

DOI

10.21007/etd.cghs.2010.0344

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