Spillovers of Nipah virus (NiV) from its pteropid bat reservoir into the human population continue to cause near-annual outbreaks of fatal encephalitis and respiratory disease in Bangladesh and India since its emergence in Malaysia over 20 years ago. The current lack of effective antiviral therapeutics against NiV merits further testing of compound libraries against NiV using rapid quantitative antiviral assays. The development of recombinant henipaviruses expressing reporter fluorescence and/or luminescence proteins has facilitated the screening of such libraries. In this chapter, we provide a basic protocol for both types of reporter viruses. Utilizing these live NiV-based reporter assays requires modest instrumentation and sidesteps the labor-intensive steps associated with traditional cytopathic effect or viral antigen-based assays.
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