Ross River Virus Interaction with the Type I IFN Pathways

Abstract

Ross River virus (RRV) belongs to the genus Alphavirus and is a medically important arbovirus that causes musculoskeletal disease in humans with symptoms such as arthralgia, arthritis and myalgia. Disease symptoms consistent with RRV infection were first recorded in 1928 in Australia. Currently, with approximately 5,000 cases of RRV infection reported each year in Australia, RRV is the most widely spread arbovirus throughout the South Pacific region. At present there are no specific therapeutics or vaccines available. RRV disease is treated with analgesics and non-steroidal anti-inflammatory drugs to provide symptomatic relief. Therefore, it is important to investigate RRV disease mechanisms so as to better understand disease pathogenesis, which could lead to identifying potential targets for therapeutic intervention. The host Type I interferon (IFN) system is the primary innate antiviral defence mechanism. The antiviral effects of type I IFN act to both suppress viral replication and modulate innate and adaptive immune responses during viral infection. However, the interplay between the host type I IFN responses and alphavirus infection is currently poorly understood. This thesis focuses on the role of type I IFN system in RRV infection and disease pathogenesis.