Title: Identification of Intracellular Trafficking Signals Contained Within the Vaccinia Virus F13L Protein

The F13L protein is the major envelope antigen of vaccinia virus, the prototypic member of the Orthopoxvirus genus. F13L is 372 residues in length and is essential for the formation of wrapped forms of virus. F13L contains a number of potential functional domains including a palmitylation site, a phospholipase domain and several tyrosine-based sorting signals (YxxΦ) including three YxxI motifs and a canonical YxxL late (L) domain-like motif. L domains have been identified in several other viruses, including HIV and EIAV, and function in the assembly and release of viral particles from infected cells. Since F13L is required for the formation of wrapped viral particles, it was hypothesized that one or more of these tyrosine-based motifs may possess L domain activity. Sequence analysis revealed that the YxxL motif is very highly conserved throughout the Chordopoxvirus subfamily suggesting that this sequence may convey some biological advantage to the virus. In contrast, the YxxI domains were much less conserved. A trans complementation assay was developed to analyze which residues withi