Identification of nucleolin as a cellular receptor for human respiratory syncytial virus

Tayyari, F., et al. 2011. Nat Med 17, 1132-1135.

speaker：Chan- Yi Su (蘇展儀)                                    Time：15:00~16:00 May. 16, 2011

commentator：Shun-hua Chen (陳舜華老師)             Place：Room 601

Abstract

Human respiratory syncytial virus (RSV) is a common cause of respiratory tract infections worldwide. There’s no efficacious treatment or vaccine available, and the passive immunoprophylaxis using RSV-specific antibodies is expensive and limited to those high risk patients. Therefore, identification of new cellular targets for the development of alternative RSV-specific interventions is needed. Several molecules have been proposed as RSV receptors; however, none has been validated as a functional receptor. To research for candidate RSV receptors, the authors implemented a virus overlay protein binding assay (VOPBA) and identified a direct binding between host-cell nucleolin and RSV. In the follow-up experiments, they further found that RSV interacts with nucleolin via the virus fusion envelope glycoprotein and binds specifically to nucleolin at the apical cell surface. Decreased RSV infection was observed in neutralization experiments using nucleolin-specific antibodies in competition assays, and upon siRNA knocking down of nucleolin expression. Spodoptera frugioerda Sf9 insect cells, which have been proposed to lack a cellular RSV receptor, were made permissive to RSV infection by exogenous expression of human nucleolin. An in vivo study using RNAi-mediated knockdown of lung nucleolin caused a significant reduction of RSV infection in mice. Immunohistochemical staining of RSV-infected mouse lung tissue showed overlap of RSV and nucleolin signals. In sum, this study implicates nucleolin as a functional cellular receptor for RSV infection and may provide a new target for future development of anti-RSV intervention.

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