The familiarity of the FDA with adenovirus gene delivery technology and approved cIFN-a protein support the development of DEF201 for clinical use. An important step in the development process is the safety/toxicology testing in rodents, which is presently underway. In our studies, the highest dose of 10 8 pfu of DEF201 administered by the i.n. route appeared to be well-tolerated in hamsters despite evidence of weight loss. They did not appear visibly ill, but clearly the treatment was having some effect that possibly led to reduced food and water consumption consistent with mild toxicity seen with IFN-a therapy. The i.n. delivery route is designed to circumvent pre-existing immunity to adenovirus type 5 in humans [21, 34] , and may limit systemic inflammation that could occur by parenteral administration of large numbers of adenovirus particles. Ultimately, the production of a shelf-stable, powdered formulation of DEF201 for easy i.n. administration and long-term storage would be ideal for stock-piling in the event of the need for mass distribution due to intentional release or (re)emerging disease outbreaks of arena or other viral etiology. Protein Disulfide Isomerase and Host-Pathogen Interaction Reactive oxygen species (ROS) production by immunological cells is known to cause damage to pathogens. Increasing evidence accumulated in the last decade has shown, however, that ROS (and redox signals) functionally regulate different cellular pathways in the host-pathogen interaction. These especially affect (i) pathogen entry through protein redox switches and redox modification (i.e., intra- and interdisulfide and cysteine oxidation) and (ii) phagocytic ROS production via Nox family NADPH oxidase enzyme and the control of phagolysosome function with key implications for antigen processing. The protein disulfide isomerase (PDI) family of redox chaperones is closely involved in both processes and is also implicated in protein unfolding and trafficking across the endoplasmic reticulum (ER) and towards the cytosol, a thiol-based redox locus for antigen processing. Here, we summarise examples of the cellular association of host PDI with different pathogens and explore the possible roles of pathogen PDIs in infection. A better understanding of these complex regulatory steps will provide insightful information on the redox role and coevolutional biological process, and assist the development of more specific therapeutic strategies in pathogen-mediated infections. Host cells have the ability to cope with the progression and severity of infection in response to different types of pathogen. On the other hand, numerous mechanisms have evolved that support the use of the host cell machinery to facilitate pathogen survival and multiplication. Such co-evolutionary processes are directly affected by different physicochemical factors within different cell compartments, both in the host and in pathogen. For instance, pH critically affects antigen stability of the influenza virus which modulates endosome acidity that attenuates its own infection [1] . ROS (and Reactive Nitrogen Species) production and the redox state of different cell compartments are also critically involved in cellular hostparasite interaction. Among the many redox sensitive proteins that are altered during the course of different infections, protein disulfide isomerase (PDI-) mediated redox switches have been associated with pathogen attachment-internalization, antigen processing in the ER/phagosome, and the regulation of ROS production by Nox family enzymes. Thus, PDI emerges as a ubiquitous redox protein that regulates different steps of diverse infection processes. Several pathogens also have their own PDI that act as an important virulence factor (Table 1 ). Other redox modifications directly mediated by ROS and especially via nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS), which is abundant in phagocytic cells, have been reviewed elsewhere [2, 3] and are not considered in this article. Below, the main cellular redox aspects of host and pathogen PDI will be discussed.