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Our immune system can launch a quick defence against a large number of unforeseen viruses. This front line of defence restricts virus spread and buys time for our body to develop specific and long-lasting immunity. One of the major weapons in this defence system is interferons (IFNs) that are proteins with broad-spectrum antiviral activity. Therefore, understanding the interplay between IFNs and viral agents may provide an insight into the development of a single medical countermeasure effective agasint multiple viral agents. As an initial step to tap the IFNs for developing therapeutics against multiple strains of alphaviruses, this memo presents recent advances in studying the role of IFNs in alphavirus pathogenesis. I first review IFNs, then focus on IFN responses against three BW agents in the alphavirus family: Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV). I conclude with discussion of how to apply this knowledge for therapeutic and vaccine development.