Date of Award
Master of Science (MS)
Jonathan A. McCullers Ph.D.
Julia Hurwitz, Ph.D. Pat Ryan, Ph.D.
glycosylation, hemagglutinin, influenza, neutralizing antibodies, T-cells
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.
Wanzeck, Keith C. , "Glycan Shielding of the Influenza Virus Hemagglutinin Elicits Evasion of the Adaptive Immune Response and T-Cell-Driven Pathology" (2010). Theses and Dissertations (ETD). Paper 280. http://dx.doi.org/10.21007/etd.cghs.2010.0344.