tailieunhanh - Báo cáo y học: " Diametrically opposed effects of hypoxia and oxidative stress on two viral transactivators"

Diametrically opposed effects of hypoxia and oxidative stress on two viral transactivators | Washington et al. Virology Journal 2010 7 93 http content 7 1 93 VIROLOGY JOURNAL RESEARCH Open Access Diametrically opposed effects of hypoxia and oxidative stress on two viral transactivators AmberT Washington 1 Gyanendra Singh2 and Ashok Aiyar 1 2 Abstract Background Many pathogens exist in multiple physiological niches within the host. Differences between aerobic and anaerobic conditions are known to alter the expression of bacterial virulence factors typically through the conditional activity of transactivators that modulate their expression. More recently changes in physiological niches have been shown to affect the expression of viral genes. For many viruses differences in oxygen tension between hypoxia and normoxia alter gene expression or function. Oxygen tension also affects many mammalian transactivators including AP-1 NFkB and p53 by affecting the reduced state of critical cysteines in these proteins. We have recently determined that an essential cys-x-x-cys motif in the EBNA1 transactivator of Epstein-Barr virus is redox-regulated such that transactivation is favoured under reducing conditions. The crucial Tat transactivator of human immunodeficiency virus HIV has an essential cysteine-rich region and is also regulated by redox. Contrary to EBNA1 it is reported that Tat s activity is increased by oxidative stress. Here we have compared the effects of hypoxia oxidative stress and cellular redox modulators on EBNA1 and Tat. Results 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. Conclusions We conclude that oxygen partial pressure and oxidative stress affects the functions of EBNA1 and Tat in a dramatically opposed