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Arthritogenic alphaviruses, including Chikungunya virus (CHIKV), Ross River virus (RRV), Barmah Forest virus (BFV), Mayaro virus (MAYV), and O'nyong'nyong virus (ONNV), are responsible for debilitating musculoskeletal diseases such as arthralgia, arthritis, and myalgia. These conditions often persist chronically, significantly impairing affected individuals for months or years. Alphaviruses are recognised as emerging pathogens, with their incidence on the rise as they spread to new host populations. Alphaviruses such as RRV and BFV, are endemic to Australia and the Southern Pacific islands, with around 5,000 reported RRV and 1,000 reported BFV cases in Australia annually. In contrast, CHIKV has a global distribution, with cases reported in more than 110 countries across Asia, Africa, Europe, and the Americas since 2005. Notable outbreaks include over 200,000 cases on La Reunion island in 2006, an estimated of about 1.3 million cases in India between 2005-2006, over 2 million cases in the Americas from 2013-2016, around 15,000 cases in Thailand between 2018-2019, and around 80,000 cases in Paraguay between 2022-2023. CHIKV has been identified as a virus to cause the next pandemic. The global impact of CHIKV infection is estimated at over 106,000 disability-adjusted life years (DALYs) annually, making it one of the World Health Organization's top priority Emerging Infectious Diseases and ranking fourth in public health need according to the Coalition for Epidemic Preparedness Innovations. Despite posing a significant public health threat, there is currently no licensed vaccine or available therapy for arthritogenic alphavirus diseases. Understanding host factors is crucial for developing therapeutic strategies. Researchers have made substantial progress in identifying and studying various host factors that play pivotal roles in alphavirus pathogenesis. Although many of these factors have been extensively characterised,knowledge gaps persist, particularly regarding MXRA8 and FHL1. Therefore, this thesis focused on investigating and characterising the roles played by host factors MXRA8 and FHL1 in alphavirus diseases. [...]