Cell-Specific Inhibition of Interferon Production by Rotavirus

Rotavirus (RV) is a leading cause of diarrhoea in young children. In 2016, rotavirus-related death was estimated around 128,500, with 258,173,300 episodes of diarrhoea in children below 5 years. Although extra-intestinal rotavirus infection is limited, the spread of the virus can cause seizures and pancreatitis. Rotavirus non-structural protein 1 (NSP1) is responsible for viral evasion of the innate immune system, the first line of defence against invading pathogens. The activated immune system produces interferon (IFNs), a cytokine that drives expression of antiviral effectors, known as IFN-stimulated genes (ISGs). The studies reported in this thesis investigate the differences in rotaviral infection of two human cell lines; the intestinal (Caco-2) and the alveolar basal (A549) epithelial cells. Our findings confirmed the potential ability of the virus to establish extra-intestinal infection in A549 cells. Furthermore, our results showed up-regulated IFNs and ISGs transcription in RV-infected A549 cells, which was absent in infected Caco-2 cells. While NSP1 was known to mediate degradation of IRF3 to antagonise the host immune response, the differences observed between Caco-2 and A549 cells were not due to IRF3 degradation. This study highlights the distinct transcriptional profile following virus replication; Caco-2 cells infected with replication-deficient RV induced transcription of IFNs and ISGs to a similar extent as infected A549 cells. However, this response was abrogated only in Caco-2 cells in the presence of replication-competent RV, suggesting differences in virus-host interactions that allowed A549 cells to produce IFNs.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Biological Science

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2019

Author dc:creator

• Shahrudin, Shabihah

Advisor dc:contributor.advisor

• Taylor, John

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/53198

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/53198