Abstract:
DING proteins have a characteristic N-terminal DINGGG- sequence and have been isolated from all kingdoms, although eukaryotic DING genes remain elusive. Recently, a DING protein isolated from St. Johns Wort (p27SJ ) was found to inhibit HIV-1 transcription and replication, with the inhibition of the human transcription factor C/EBP being a proposed mechanism. Pseudomonas DING proteins share a high sequence identity with p27SJ and were therefore likely to also have anti-HIV activity. In this study, the biological and anti-HIV activities of Pseudomonas DING proteins were investigated, with speci c focus on e ects on the activity of transcription factors involved in HIV-1 replication. Initial experiments attempted to evaluate the e ect of DING proteins on C/EBP but no e ects were observed using the chosen experimental techniques. DING proteins were found to have signi cant e ects on NF B activity and the expression of NF B-dependent genes. They were then tested for their potential to inhibit HIV-1 but the results did to re ect their e ects on NF B and it was evident that other factors were involved. The e ect of DING proteins on the interferon response may be important in this area. Due to the di erences in activity of DING proteins, potential biologically active peptides were able to be determined. This study demonstrates that DING proteins are able to manipulate human transcription, and raises the possibility that they are bacterial virulence factors that have roles in the pathogenesis of many human diseases. It also demonstrates the potential of DING proteins as novel agents in the treatment of HIV-1 infection.