Document Type

Dissertation - Open Access

Award Date

2017

Degree Name

Doctor of Philosophy (PhD)

Department / School

Biology and Microbiology

First Advisor

Feng Li

Abstract

Influenza B virus (IBV) is an important pathogen that infects humans and causes seasonal influenza epidemics. By using next-generation sequencing (NGS) approach, we analyzed total mRNAs extracted from A549 cells infected with B/Brisbane/60/2008, and identified four defective genomes in IBV with two from the polymerase basic subunit 1 (PB1) segment and the other two from the matrix (M) segment. Each of them can potently inhibit the replication of IBV. One derived from PB1 segment was able to interfere modestly with influenza A virus (IAV) replication. The productions of the four defective RNAs are not dependent on the cell types. The important initial insights into IBV defective genomes can be further explored toward better understanding of the replication, pathogenesis, and evolution of IBV. The second study demonstrated that influenza D virus (IDV) is more efficient in recognizing both human Neu5,9Ac2 and non-human Neu5Gc9Ac receptors than influenza C virus (ICV). ICV prefers human Neu5,9Ac2 over non-human Neu5Gc9Ac. The results reveal that IDV and ICV diverge in communicating with both O-acetyl group at the C9 position and acetyl/glycolyl groups at the C5 position in terminal 9-carbon SAs. Our findings provide evidence that IDV has acquired the unique ability to infect and transmit among agricultural animals that are enriched in Neu5Gc9Ac, in addition to pose a zoonotic risk to humans only expressing Neu5,9Ac2. Characterization of a contemporary human ICV is needed. C/Victoria/2/2012 (C/Vic) isolated in 2012 was used in this study. Phylogenetic studies demonstrated that C/Vic is a reassortant virus composed of segments derived from multiple ICV lineages or strains, which evolved independently. We identified two mutations in the 170-loop of the HEF protein around the receptor binding pocket as a possible antigenic determinant responsible for the discrepant hemagglutinin inhibition results. C/Vic replicates more efficiently at the cool temperature, which should be further investigated toward elucidating the molecular determinants of temperature-dependent growth. The study on this contemporary ICV shall aid in the further investigation of biology, evolution, and pathogenesis of ICV.

Library of Congress Subject Headings

Influenza viruses.
Viral genetics.

Description

Includes bibliographical references (pages 142-146)

Format

application/pdf

Number of Pages

162

Publisher

South Dakota State University

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Rights Statement

In Copyright