Date of Award

12-2016

Document Type

Thesis

College

College of Arts and Sciences

Degree Program

Biology

Degree Name

Master of Science

Thesis Advisor

Dr. Kristi Westover

Committee Member

Dr. Matthew Stern

Committee Member

Dr. Matthew Heard

Keywords

hantavirus, nucleocapsid, CTL, epitope

Abstract

Hantaviruses pathogenic to humans are exclusive to rodents. Typically each hantavirus is associated with only one host species. Due to their close association, the geographical distributions are the same. Old World species, such as Hantaan hantavirus and Puumala hantavirus, induce symptoms described as the Hemorrhagic Fever with Renal Syndrome (HFRS). The New World hantaviruses, such as Andes hantavirus and Sin Nombre hantavirus, share a suite of symptoms that have been described as Hantavirus Pulmonary Syndrome (HPS). In this study, 16 well-characterized cytotoxic T lymphocytes (CTL) epitopes of the nucleocapsid (N) protein were identified from the literature.

These 16 antigenic regions are reportedly CD8+ epitopes showing reactivity to one or more hantaviruses. A phylogenetic analysis was used to identify closely related sequences called sister pairs. The number of nonsynonymous differences per nonsynonymous site (pN) and the number of synonymous differences per synonymous site (pS) were computed. Comparisons were then made between New World and Old World groups, as well as between pathogenic and non-pathogenic groups. It was expected that there would be evidence of viral escape, measured as elevated pN to pS means in the well characterized CTL epitopes of the N protein. However, evidence of CTL escape was not observed in this study. None of the epitopes exhibited positive selection. The mean pS value was greater than the mean pN value in all cases. The N protein appears to be have been highly conserved throughout most hantaviruses. Numerous epitopes did show evidence of possible negative, or purifying, selection. Because of genus specificity of the various epitopes, future studies comparing substitution rates within genera could be insightful.

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