The resolution of the N 0-P X-ray structures of Nipah virus ( 8), measles virus (MeV) ( 9), human metapneumovirus (HMPV) ( 10), Ebola virus ( 11), Marburg virus ( 12), vesicular stomatitis virus (VSV) ( 13), and parainfluenza virus 5 (PIV5) ( 14) confirmed this hypothesis and brought evidence that these viruses share a similar mechanism. Bioinformatic studies have suggested that all P proteins of the Mononegavirales use their N-terminal subdomain (P N-ter) as a means to maintain N in its monomeric RNA-free N 0 form ( 7). Prior to the encapsidation of genomic RNA, N is kept in an assembly-competent form known as N 0 by binding to the chaperone phosphoprotein (P) until it is delivered to nascent synthesized viral RNA ( 4).īecause of the high propensity of nucleoprotein N to interact with RNA and oligomerize, the isolation and characterization of the N 0-P complex are challenging and have not yet been successfully achieved, and the molecular mechanisms involved in the transition from the N 0-P complex to the N-RNA nucleocapsid still remain to be elucidated. These two protein-protein interactions mediated by the CTD- and NTD-arms hold the protomers together and are therefore critical for the oligomerization of N. 1), that play a key role in the formation of the nucleocapsid: the N i − 1 protomer CTD-arm binds atop of the N i protomer CTD, and simultaneously, the N i + 1 protomer NTD-arm binds against the flank of the N i protomer ( i is the middle subunit of three adjacent N protomers). The NTD and the CTD have N- and C-terminal extensions, named NTD-arm and CTD-arm, respectively ( Fig. The nucleoprotein oligomerizes and enwraps the genomic RNA with its two globular domains, the N-terminal domain (NTD) and the C-terminal domain (CTD), linked through a hinge region ( 6). Both the neosynthesized antigenome and genome strands are encapsidated by nucleoprotein N to form ribonucleocapsids (RNCs). The newly synthesized antigenome strand serves as the template for further copies of the genomic RNA. To replicate, the negative-strand RNA genome must be converted into the antigenome positive strand by the RNA-dependent RNA L polymerase. The genomic RNA of RSV is 15 kb in length and contains 10 tandemly linked genes that encode 11 proteins in the following order: the nonstructural NS1 and NS2, nucleoprotein (N), phosphoprotein (P), matrix (M), small hydrophobic (SH), glycoprotein (G), fusion (F), M2-1 and M2-2 (bicistronic), and large (L) proteins. RSV is an enveloped negative-strand RNA virus that belongs to the Mononegavirales order and that is a member of the Pneumovirus family ( 5). As a result, 60% of at-risk children remain untreated, and no efficient therapy is available to treat the adult population. However, its limited efficacy (approximately 50%) and high cost (€5,000 per treatment) limit its use to preterm infants with bronchopulmonary dysplasia and chronic respiratory disease and newborns with congenital heart disease ( 2). The current standard of care consists of prophylactic treatment of at-risk infants with palivizumab (Synagis), a monoclonal antibody that is administered monthly as an injectable during the peak season of infection (typically, November to March in Europe and in the United States). In addition, the virus is also increasingly recognized as an important pathogen in the elderly population as well as in bone marrow transplant recipients ( 4). A recent study performed by Pneumonia Etiology Research for Child Health (PERCH) across 7 countries revealed that RSV was the reason for hospitalization for 31% of all children hospitalized with severe pneumonia ( 3). In the United States, it has been estimated that RSV is responsible for 86,000 child hospitalizations per year, with an estimated cost of $394 million ( 2). In 2005, RSV caused almost 34 million cases of lower respiratory infections in children under 5 years of age, with 3 to 10% of them requiring hospitalization, accounting for 45% of the total child admissions ( 1). Respiratory syncytial virus (RSV) is very contagious and represents the main cause of severe acute respiratory tract illness in young children worldwide.
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