In the Spotlight…
Molecular Genetics and Microbiology
Graduate Student Amanda Ullman

Dissertation Research:

The focus of my research involves the study of an adenovirus early protein, early region 4 (E4) open reading frame 3 (ORF3). We have found that this protein is required for viral DNA (vDNA) replication during the interferon (IFN)-induced antiviral state. Furthermore, we have determined that an E4 ORF3 requirement for replication during the IFN response is functionally conserved among evolutionarily divergent Ad serotypes.

We have ascertained that the protein’s ability to rearrange a nuclear subdomain, the PML oncogenic domain (POD), into track structures correlates to the E4 ORF3-mediated inhibition of an antiviral defense. This is particularly interesting, as PODs are targeted for disruption by a variety of viruses. In many cases, this disruption impedes antiviral effects. Thus, we have provided evidence that further strengthens the link between the POD and innate immunity. This function of the E4 ORF3 protein during the IFN-induced antiviral state was also demonstrated to be independent of the protein’s ability to sequester the cellular sensor of double strand DNA breaks, the Mre11-Rad50-NBS1 (MRN) complex, into track structures.

Ongoing work is being conducted to elucidate the specific antiviral mechanisms antagonized by the E4 ORF3 protein during the IFN response. Here, a proteomics approach is being employed, utilizing recombinant E4 ORF3 to determine which cellular proteins are bound by E4 ORF3 exclusively during the antiviral state. The identification of these cellular binding partners should aid in understanding the antiviral mechanism undermined by the adenovirus E4 ORF3 protein.

B.S., Microbiology, McGill University
Advisor: Dr. Patrick Hearing

Recipient of the 2006 Distinguished Service Award, Department of Molecular Genetics and Microbiology and the 2007 Abrahams Award for Outstanding Achievement by a Graduate Student

Publications:

Ullman, A.J., Reich, N.C., and Hearing, P. (2007) The adenovirus E4 ORF3 protein inhibits the interferon-mediated antiviral response. J. Virol. 81: 4744-4752. (Article of Significant Interest Selected from this Issue by the Editors)