Quantitative Proteomic Analysis of A549 Cells Infected with Human Respiratory Syncytial Virus

Munday, Diane C.; Emmott, Edward; Surtees, Rebecca; Lardeau, Charles-Hugues; Wu, Weining; Duprex, W. Paul; Dove, Brian K.; Barr, John N.; Hiscox, Julian A.

Changes in the abundance and localization of mitochondrial proteins such as Toms (Fig. 7, B and C) , VDACs (Fig. 8A) , and PHBs (Fig. 8B) may be linked to a number of factors relating to the immune response, antiviral state, and viral infection. IPA defines mitochondrial dysfunction as anything (genetic or environmental) that interferes with the regulation of reactive oxygen species (ROS) causing the superoxide to overpower the antioxidant system. ROS are potent elements in the mitochondrial antimicrobial defense system, and mitochondria may participate in the innate immune response by triggering the production of ROS (81) . However, as is the case in the IFN pathway, microbes may have evolved strategies to manipulate such defense mechanisms, and any alterations in mitochondrial function may affect the immune response of cells to virus infection. For example, HCV is able to block the mitochondrial antiviral signaling protein (found on the outer membrane of the mitochondria) downstream signaling pathway, which leads to the expression of IFN ␤, thereby enabling HCV to evade host immunity (85) . Furthermore, human cytomegalovirus has been shown to perturb many cellular processes that promote the release of proapoptotic molecules such as cytochrome c (86) .