The synthetic bacterial lipopeptide Pam3CSK4 modulates respiratory syncytial virus infection independent of TLR activation

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 RSVA2- 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-signaling capacity that also modulate RSV infection, whereas Pam3CSK4-reminiscent TLR1/2 agonists did not, and conclude that modulation of infection is independent of TLR activation. A similar TLR-independent enhancement of infection could also be demonstrated for wild-type RSV strains, and for HIV-1, measles virus and human metapneumovirus. We show that the effect of Pam3CSK4 is primarily mediated by enhanced binding of RSV to its target cells. The Npalmitoylated cystein

Antiviral Immune Responses by Human Langerhans Cells and Dendritic Cells in HIV-1 Infection

The main route of human immunodeficiency virus-1 (HIV-1) infection is via unprotected sexual intercourse, and therefore, vaginal tissues and male foreskin are viral entry sites. Langerhans cells (LCs) and dendritic cells (DCs) are amongst the first immune cells encountering HIV-1 since these cells line these mucosal tissues. Both LCs and DCs are equipped with specific pattern recognition receptors that not only sense pathogens, but induce specific immune responses against these pathogens. LCs express the C-type lectin receptor langerin, which provides protection against HIV-1 infection. In contrast, DCs express the C-type lectin receptor DC-SIGN, which facilitates capture as well as infection of DCs and subsequent transmission to CD4(+) T cells. This chapter gives an update on immune responses elicited against viruses and sheds a light on different immune mechanisms that are hijacked by HIV-1 to infect the host. HIV-1 infection ultimately leads to the world-wide pandemic acquired immunodeficiency syndrome (AIDS