Date of Award
Master of Science (MS)
Jonathan A. McCullers Ph.D.
Julia Hurwitz, Ph.D. Pat Ryan, Ph.D.
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.