the synthetic bacterial lipopeptide pam3csk4 modulates respiratory syncytial virus infection independent of tlr activation合成细菌lipopeptide pam3csk4调节呼吸道合胞病毒感染无关的tlr激活.pdfVIP

The Synthetic Bacterial Lipopeptide Pam3CSK4 Modulates Respiratory Syncytial Virus Infection Independent of TLR Activation 1 1 1 ¨ 1 ¨ 2 D. Tien Nguyen , Lot de Witte , Martin Ludlow , Selma Yuksel , Karl-Heinz Wiesmuller , Teunis B. H. 3 1 1 Geijtenbeek , Albert D. M. E. Osterhaus , Rik L. de Swart * ¨ 1 Department of Virology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands, 2 EMC microcollections GmbH, Tubingen, Germany, 3 Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Abstract Respiratory syncytial virus (RSV) is an important cause of acute respiratory disease in infants, immunocompromised subjects and the elderly. However, it is unclear why most primary RSV infections are associated with relatively mild symptoms, whereas some result in severe lower respiratory tract infections and bronchiolitis. Since RSV hospitalization has been associated with respiratory bacterial co-infections, we have tested if bacterial Toll-like receptor (TLR) agonists influence RSV- A2-GFP infection in human primary cells or cell lines. The synthetic bacterial lipopeptide Pam3-Cys-Ser-Lys4 (Pam3CSK4), the prototype ligand for the heterodimeric TLR1/TLR2 complex, enhanced RSV infection in primary epithelial, myeloid and lymphoid cells. Surprisingly, enhancement was optimal when lipopeptides and virus were added simultaneously, whereas addition of Pam3CSK4 immediately after infection had no effect. We have identified two structurally related lipopeptides without TLR-signa