Abstract
In this review we propose a partially hypothetical model of respiratory syncytial virus (RSV) binding and entry to the cell that includes the recently discovered RSV receptor nucleolin, in an attempt to stimulate further inquiry in this research area. RSV binding and entry is likely to be a two-step process, the first involving the attachment of the virus to the cell membrane, which may be enhanced by electrostatic interactions with cellular glycoproteins/heparin and the viral G protein, and the second involving fusion to the cell membrane mediated by the viral F protein and a specific cellular fusion receptor. With our recent discovery of nucleolin as a functional fusion receptor for RSV, comes the possibility of a number of new approaches to the development of novel strategies for RSV prophylaxis and therapy, as well as raising some new questions concerning the pathobiology of RSV infection and tropism.
Highlights
Human respiratory syncytial virus (RSV) is found ubiquitously and a major cause of acute lower respiratory tract infections in children leading to hospitalization and occasionally death [1]
As will be discussed in further detail below, we propose that RSV binding and entry into cells is likely to be at least a two-step process: first, attachment of the virus to the cell membrane mediated by electrostatic interactions with cellular glycoproteins/heparin and the viral G protein, and secondly, fusion to the cell membrane mediated by the viral F protein and a specific cellular fusion receptor
The biological plausibility of RSV-nucleolin interaction in infection was confirmed in vitro and in vivo through a series of experiments that included: visualization of RSV-nucleolin co-localization on the cell surface by use of confocal fluorescence microscopy; decreased RSV infection of cells pre-treated with nucleolin-specific antibody and when cellular nucleolin expression was silenced by use of RNA interference, or when virus was incubated with soluble recombinant nucleolin prior to being added to cell cultures; increased RSV infection of a non-permissive cell type (Sf9) [36] that had been transfected with the human nucleolin gene and which showed ectopic expression of human nucleolin protein on the cell surface; decreased RSV infection of mouse lung, in animals that were pre-treated with short-interfering RNA of mouse nucleolin, delivered intranasally prior to RSV
Summary
Human respiratory syncytial virus (RSV) is found ubiquitously and a major cause of acute lower respiratory tract infections in children leading to hospitalization and occasionally death [1]. RSV causes disease in adults, in the elderly and in the immunocompromised [2]. RSV is a negative-polarity, enveloped, single-stranded RNA virus from the Paramyxoviridae family. In spite of the fact that the virus was discovered in 1956, a safe, effective vaccine for RSV has remained elusive [3]. In this article we discuss aspects related to the discovery of nucleolin as a functional fusion receptor for RSV and propose a revised model for RSV fusion at the cell surface that incorporates nucleolin. We discuss the implications this discovery has on the pathobiology of RSV infections and the development of novel prophylactic and therapeutic strategies
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
