The Garcia-Sastre Laboratory is focused on exploring virus-host interactions with an emphasis on virus regulation of innate and adaptive immune responses. The outcome of these interactions not only determines disease severity but also influences the development of protective immunity resulting from viral infection and/or vaccination. The team has developed several techniques (reverse genetics), which allow for the genetic manipulation of the genomes of several virus families including influenza virus and Newcastle disease virus. Other viruses being studied include Zika virus, Dengue virus, West Nile virus, and Crimean-Congo hemorrhagic fever virus. These techniques are currently being used in several research areas including: i) characterization of virus-encoded virulence factors, ii) identification of virus-encoded antagonists of the interferon system, iii) virus replication and gene expression, iv) immune regulation of influenza replication, and v) vaccine development. Reverse genetics are also being utilized to generate virus vectors based on influenza virus and Newcastle disease virus. These viruses are effective inducers of humoral and cellular immune responses. Live attenuated influenza virus vaccines are being generated by genetic modification of the influenza virus-encoded interferon antagonist that was originally identified by the laboratory. Also, recombinant viruses can be produced that express protective antigens of other pathogens for which no safe attenuated vaccine strains are available.