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The impact of respiratory syncytial virus (RSV) on morbidity and mortality is significant in that it causes bronchiolitis in infants, exacerbations in patients with obstructive lung disease, and pneumonia in immunocompromised hosts. RSV activates protein kinase R (PKR), a cellular kinase relevant to limiting viral replication (Groskreutz, D. J., Monick, M. M., Powers, L. S., Yarovinsky, T. O., Look, D. C., and Hunninghake, G. W. (2006) J. Immunol. 176, 1733-1740). It is activated by autophosphorylation, likely triggered by a double-stranded RNA intermediate during replication of the virus. In most instances, ph-PKR targets the a subunit of eukaryotic translation initiation factor 2 (eIF2α) protein via phosphorylation, leading to an inhibition of translation of cellular and viral protein. However, we found that although ph-PKR increases in RSV infection, significant eIF2α phosphorylation is not observed, and inhibition of protein translation does not occur. RSV infection attenuates eIF2α phosphorylation by favoring phosphatase rather than kinase activity. Although PKR is activated, RSV sequesters PKR away from eIF2α by binding of the kinase to the RSV N protein. This occurs in conjunction with an increase in the association of the phosphatase, PP2A, with eIF2α following PKR activation. The result is limited phosphorylation of eIF2α and continued translation of cellular and viral proteins. [ABSTRACT FROM AUTHOR]

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are responsible for a large proportion of the health care dollar expenditure, morbidity, and mortality related to COPD. Respiratory infections are the most common cause of acute exacerbations, but recent evidence indicates that the importance of respiratory syncytial virus (RSV) infection in COPD is under-appreciated. Improved detection of RSV using techniques based on the polymerase chain reaction accounts for much of the increased recognition of the importance of this virus in COPD patients. Furthermore, COPD patients may be more susceptible to RSV infection, possibly due to RSV-or immune response-induced pulmonary effects that are altered by age, environmental exposures, genetics, COPD itself, or a combination of these. However, although RSV infection occurs throughout life, viral and host factors that place COPD patients at increased risk are unclear. The complexities of RSV effects in COPD present opportunities for research with the goal of developing approaches to selectively modify damaging viral effects (e.g., altered airway function), while retaining beneficial immunity (e.g., clearance of virus) in COPD patients. This review explores the role RSV plays in acute exacerbations of COPD, the potential for RSV disease in chronic stable COPD, and newer concepts in RSV diagnosis, epidemiology, and host defense. [ABSTRACT FROM AUTHOR]