During the SARS-CoV-2 pandemic, the world scrambled to develop means to effectively treat COVID. Whereas initial efforts focused on antivirals, it soon became clear that this would not be enough. To be effective, antivirals need to be administered at a stage where inhibiting the virus can change the course of disease.
This strategy is inherently flawed for many viruses which are not only difficult to diagnose in the early stages of infection but also have a disease pathology driven by viral-triggered host response. Over the past decade, my team has shown that mosquito-transmitted alphaviral disease is largely immune-modulated. Therefore, to successfully treat alphaviral-inflammatory disease, the therapy must be ‘disease-modifying’, targeting the underlying pathophysiology of the host rather than the virus itself.
We recently employed a digital spatial imaging technique to track immune influx during infection. Analysing mouse tissues infected with two different emerging alphaviruses; chikungunya virus (CHIKV) and o’gnyong nyong virus (ONNV), we identified 16 immune markers, including PD-1, CD11b/c, FN1 and CD45, across epidermis, muscle, and bone, revealing new host-targets. We have continued to explore the role of fibronectin (FN1; a recognised DAMP) in mouse models of alphaviral disease and found that there is tissue and organ specific upregulation of FN1 in response to infection and this response also fluctuated with the kinetics of disease. As FN1 is a critical component of the extracellular matrix (ECM) and is known to contribute to tissue repair and immune response regulation it is currently being explored as a target for drug development against several critical inflammatory diseases. With mosquito-borne viruses spreading globally, effective therapeutics are crucial. Targeting the host with disease-modifying therapies and a repurposing strategy offers a chance to mitigate their impact now and in the future.