Profilin is required for viral morphogenesis, syncytium formation, and cell-specific stress fiber induction by respiratory syncytial virus

We tested three cell lines: HEp-2 (human), A549 (human), and L2 (rat). In all three, RSV grew well and produced fused cells (syncytium), and two RSV proteins, namely, the phosphoprotein P and the nucleocapsid protein N, associated with profilin. In contrast, induction of actin stress fibers by RSV occurred in HEp-2 and L2 cells, but not in A549. Knockdown of profilin by RNA interference had a small effect on viral macromolecule synthesis but strongly inhibited maturation of progeny virions, cell fusion, and induction of stress fibers.Profilin plays a cardinal role in RSV-mediated cell fusion and viral maturation. In contrast, interaction of profilin with the viral transcriptional proteins P and N may only nominally activate viral RNA-dependent RNA polymerase. Stress fiber formation is a cell-specific response to infection, requiring profilin and perhaps other signaling molecules that are absent in certain cell lines. Stress fibers per se play no role in RSV replication in cell culture. Clearly, the cellular architecture controls multiple steps of host-RSV interaction, some of which are regulated by profilin.The actin cytoskeleton plays a central role in cell motility, movement and morphology. The ability of soluble monomeric G-actin to polymerize into filamentous F-actin in a reversible manner is central to the cellular function of actin [1,2]. Rearrangement of actin is promoted rapidly by extracellular stimuli, and is facilitated by sets of actin-associated proteins, one of which is profilin [2]. It is now appreciated that a large number of cellular parasites co-opt actin for their gene expression and replication in the host cell [3,4]. Due to its primary role in pediatric respiratory disease, and the enormous human and economic toll it exacts throughout the world, the respiratory syncytial virus (RSV) and its interaction with the host cell have received serious attention. RSV is a member of the Pneumovirus genus in the Paramyxoviridae family, and contains a nonseg