Theses and Dissertations

Issuing Body

Mississippi State University

Advisor

Hanson, Larry

Committee Member

Wan, Xiu-Feng (Henry)

Committee Member

King, Jonas

Committee Member

Tao, Yizhi Jane

Date of Degree

4-30-2021

Original embargo terms

Complete embargo for 1 year

Document Type

Dissertation - Open Access

Major

Veterinary Medical Science

Degree Name

Doctor of Philosophy

College

College of Veterinary Medicine

Department

Department of Basic Sciences

Abstract

The ribonucleoprotein (RNP) complex of influenza A viruses (IAVs) is responsible for replication and transcription of viral RNA and genome, respectively. Mutations in the RNP genes have been identified to play a role in host adaptations and tissue tropisms of IAVs, and compatibility among these genes has been implicated as an important factor for facilitating reassortment of IAVs. Furthermore, mutations and reassortment can drastically impact the polymerase activities of the RNP complex in vitro. However, the simultaneous role both of these mechanisms play in enhancing or diminishing polymerase activities of divergent IAVs remains opaque, and therefore, a greater understanding of how mutations and reassortment of these genes pose potential pandemic risk. In this project, a minigenome assay was used to quantify polymerase activities of various RNP complexes (i.e., complexes containing mutations, reassortant complexes with genes from divergent IAV subtypes; etc.), and applied to a machine learning model to identify genetic features within the RNP complex that are associated with polymerase activities. Applying diverse genotypic and phenotypic data from IAV RNP complexes to a machine learning model has enhanced our understanding of various mechanisms this complex of proteins uses to facilitate viral replication and evolution of IAV.

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