“Graduate education in the department of Microbiology and Immunology at Wake Forest appealed to me on many levels. The high regard held for the university from professors at my undergraduate institution initially brought me to look at Wake Forest. However upon a visit and interviews with the faculty I was impressed with the department’s commitment to graduate education as well as each individual professors’ commitment to the students. On top of the intense commitment to students, the quality of research being performed at Wake Forest assures students amazing opportunities to make contributions to our field of study.”

Identification of the human-specific factor at the RUNX1 locus required for the function of the adenovirus E4orf6–E1B-55K protein complex

The E1B-55K and E4orf6 proteins are key regulators expressed early during adenovirus infection. These proteins form a physical complex that promotes the specific export of viral mRNAs from the nucleus while blocking the export of most cellular mRNAs. These proteins bind each other weakly in vitro. However, in the cell, the E4orf6 protein changes the localization of the E1B-55K protein from cytoplasmic to nuclear. This apparent interaction is enhanced in primate cell lines but diminished in rodent cell lines. Therefore it has been hypothesized that species-specific cellular factors mediate this apparent interaction and are necessary for the E1B-55K and E4orf6 proteins to promote late viral gene expression. Such a candidate factor has been mapped to the RUNX1 locus of human chromosome 21 using somatic cell hybrids. RUNX1 is a complex locus spanning more than 260 kb of DNA and encodes at least 12 different isoforms that are expressed from proximal and distal promoters. An immediate goal of the current research is to identify the form of RUNX1 that contributes to the function of the E4orf6–E1B-55K complex using a combination of immunofluorescence, RNAi, and a modified two-hybrid reporter system. The identification of specific host factors involved in the interaction of E4orf6 and E1B-55K will advance our understanding of the role of this complex and RUNX1 in the context of viral replication and a productive infection.