EGFR interacts with the fusion protein of respiratory syncytial virus strain 2-20 and mediates infection and mucin expression.

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2-20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2-20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2-20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2-20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from "mucogenic" strains. RSV 2-20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease

Organ Donor Management: Part 1. Toward a Consensus to Guide Anesthesia Services During Donation After Brain Death

Worldwide 715 482 patients have received a lifesaving organ transplant since 1988. During this time, there have been advances in donor management and in the perioperative care of the organ transplant recipient, resulting in marked improvements in long-term survival. Although the number of organs recovered has increased year after year, a greater demand has produced a critical organ shortage. The majority of organs are from deceased donors; however, some are not suitable for transplantation. Some of this loss is due to management of the donor. Improved donor care may increase the number of available organs and help close the existing gap in supply and demand. In order to address this concern, The Organ Donation and Transplantation Alliance, the Association of Organ Procurement Organizations, and the Transplant and Critical Care Committees of the American Society of Anesthesiologists have formulated evidence-based guidelines, which include a call for greater involvement and oversight by anesthesiologists and critical care specialists, as well as uniform reporting of data during organ procurement and recovery