%0 Journal Article %T Diametrically opposed effects of hypoxia and oxidative stress on two viral transactivators %A Amber T Washington %A Gyanendra Singh %A Ashok Aiyar %J Virology Journal %D 2010 %I BioMed Central %R 10.1186/1743-422x-7-93 %X Our results indicate that unlike EBNA1, Tat is less active during hypoxia. Agents that generate hydroxyl and superoxide radicals reduce EBNA1's activity but increase transactivation by Tat. The cellular redox modulator, APE1/Ref-1, increases EBNA1's activity, without any effect on Tat. Conversely, thioredoxin reductase 1 (TRR1) reduces Tat's function without any effect on EBNA1.We conclude that oxygen partial pressure and oxidative stress affects the functions of EBNA1 and Tat in a dramatically opposed fashion. Tat is more active during oxidative stress, whereas EBNA1's activity is compromised under these conditions. The two proteins respond to differing cellular redox modulators, suggesting that the oxidized cysteine adduct is a disulfide bond(s) in Tat, but sulfenic acid in EBNA1. The effect of oxygen partial pressure on transactivator function suggests that changes in redox may underlie differences in virus-infected cells dependent upon the physiological niches they traffic to.The human body contains multiple niches that vary greatly in oxygen tension. For example, lymph nodes have oxygen partial pressure (pO2) ranging from 10-20 Torr (1-2.5% O2) [1-3]. In contrast, peripheral blood has an average level of 10-12% oxygen [ibid, [4]]. It is known that the activity of many mammalian transactivators is sensitive to changes in oxygen tension, leading to niche-specific gene expression patterns [5-9]. For years it has been noted that oxidative conditions alter gene expression in many pathogens [10-15]. Furthermore, oxygen tension is known to affect the activity of many viral proteins, including transactivators, thus changing the outcome of viral infection [16-18].One such virus that displays this characteristic is the lymphotropic human herpesvirus, Epstein-Barr virus (EBV). EBV is latent in B-cells that exist in the peripheral circulation as non-dividing memory B-cells; within lymph nodes EBV-infected cells become proliferating blasts that secrete antibody [19,20]. The %U http://www.virologyj.com/content/7/1/93