RNA interference as an alternative preventive measure for avian influenza in poultry
Date
2014
Authors
Linke, Lyndsey M., author
Salman, Mo, advisor
Landolt, Gabriele, committee member
Olea-Popelka, Francisco, committee member
Wilusz, Jeffrey, committee member
Journal Title
Journal ISSN
Volume Title
Abstract
Avian influenza virus (AIV) is a viral pathogen that causes a wide range of disease in poultry, from subclinical to severe clinical illness and can often result in death. In 1878, AIV was first described as a disease affecting poultry. Nearly 80 years later this disease-causing agent was identified as influenza A virus and a member of the family Orthomyxoviridae. AIV was not considered a significant human pathogen until 1997, when high pathogenic AIV H5N1 emerged from the wildfowl reservoir and was directly transmitted from domestic poultry to humans. Despite a long history of outbreaks in animals, this incident propelled AIV into a globally recognized disease associated with socioeconomic and animal health consequences. Each AIV outbreak highlights ways to improve upon current control strategies and stimulates new ideas for developing novel approaches and technologies to better mitigate AIV outbreaks worldwide. AIV is a dynamic pathogen to study. Host range and adaptation, pathogenicity, pathology, molecular composition, and the epidemiology of AIV all make this virus particularly challenging to control in poultry. Vaccines against AIV are available but the protection they provide for poultry is limited, especially when administered at the onset or in the midst of an outbreak. The most efficacious vaccines must be administered subcutaneously or intramuscularly, an impediment to successfully immunizing large numbers of poultry in a short window of time. Frequently, improper storage and handling leads to vaccine failure. To elicit efficient protection the vaccine must be HA-subtype specific to the outbreak virus. Often stockpiles of vaccines become obsolete and new vaccines must be generated. This is a time consuming process and can take months to secure and additional time to disseminate and administer. In the naive animal, protective antibody production takes two to three weeks to acquire following vaccination. Even if the decision to vaccinate during an outbreak is rapid and an appropriate vaccine is available for immediate use in poultry, vaccination alone would do little to protect against the threat of infection and break the chain of transmission, especially in areas lacking appropriate biosecurity measures. These limitations convey a genuine need to develop a prophylactic that would offer universal protection against any subtype or strain of AIV and would provide rapid protection in the face of an outbreak. Using RNA interference (RNAi) methodologies, this dissertation focuses on developing an innovative antiviral prophylactic that works rapidly to protect poultry against AIV shedding and transmission. The innovation behind this prophylactic technology lies in combining RNAi with the transkingdom RNAi (tkRNAi) delivery platform. This anti-AIV technology specifically targets conserved viral gene segments using small interfering RNA (siRNA) generated and delivered to chicken mucosal respiratory tissues using the tkRNAi system. The work presented in this dissertation details the steps taken to show proof of concept for using this technology to prevent AIV replication and shedding in vitro using an avian cell model and in vivo using commercial chickens. The overarching vision for this anti-AIV technology is to provide a cost effective means to protect commercial and backyard flocks against AIV outbreaks. The long-term goal is to promote this prophylactic as a complement to vaccination with the intention of developing a more effective and robust control plan against AIV in poultry. If this technology is successful, it could be applied in the face of an outbreak to reduce the shedding and transmission of virus within poultry, between farms, and across borders, thereby improving animal health and reducing the economic impact of outbreaks worldwide. Additionally, this work could provide the framework and valuable evidence for developing a similar anti-influenza prophylactic for humans.
Description
Rights Access
Subject
antiviral
prophylactic
siRNA
avian influenza
poultry
RNA interference