Eastern equine encephalitis virus (EEEV), a mosquito-borne member of the Alphavirus genus of the Togaviridae family, is among the deadliest of the mosquito-borne viruses. EEEV possesses a single-stranded, positive-sense RNA genome of approximately 11.7 kb. The four viral nonstructural proteins (nsP1-4) are produced from the full-length genomic RNA as a polyprotein and carry out functions important for viral RNA synthesis and polyprotein processing. A second polyprotein, translated from the 26S subgenomic mRNA, gives rise to the three major structural proteins, namely, the capsid and the two envelope proteins, E1 and E2. The envelope proteins are involved in receptor recognition, virus attachment, penetration, and membrane fusion during viral entry. These proteins also cooperate with the capsid during viral assembly and release.