Glycan Shielding of the Influenza Virus Hemagglutinin Elicits Evasion of the Adaptive Immune Response and T-Cell-Driven Pathology

<p>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.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Biomedical Sciences

Year dc:date.available

2010

Author dc:creator

• Wanzeck, Keith C.

Contributors dc:contributor

• Jonathan A. McCullers Ph.D.

• glycosylation
• hemagglutinin
• influenza
• neutralizing antibodies
• T-cells
• Diseases
• Influenza Humans
• Medical Molecular Biology
• Medical Sciences
• Medicine and Health Sciences
• Virus Diseases

Repository record dc:identifier

https://dc.uthsc.edu/dissertations/280

OAI identifier oai:identifier

oai:dc.uthsc.edu:dissertations-1289