scholarly journals The 24-Angstrom Structure of Respiratory Syncytial Virus Nucleocapsid Protein-RNA Decameric Rings

2007 ◽  
Vol 81 (17) ◽  
pp. 9519-9524 ◽  
Author(s):  
Kirsty MacLellan ◽  
Colin Loney ◽  
R. Paul Yeo ◽  
David Bhella

ABSTRACT Respiratory syncytial virus (RSV), a nonsegmented, negative-sense RNA-containing virus, is a common cause of lower respiratory tract disease. Expression of RSV nucleocapsid protein (N) in insect cells using the baculovirus expression system leads to the formation of N-RNA complexes that are morphologically indistinguishable from viral nucleocapsids. When imaged in an electron microscope, three distinct types of structures were observed: tightly wound short-pitch helices, highly extended helices, and rings. Negative stain images of N-RNA rings were used to calculate a three-dimensional reconstruction at 24 Å resolution, revealing features similar to those observed in nucleocapsids from other viruses of the order Mononegavirales. The reconstructed N-RNA rings comprise 10 N monomers and have an external radius of 83 Å and an internal radius of 40 Å. Comparison of this structure with crystallographic data from rabies virus and vesicular stomatitis virus N-RNA rings reveals striking morphological similarities.

2014 ◽  
Vol 89 (3) ◽  
pp. 1564-1578 ◽  
Author(s):  
Yung-Chang Su ◽  
Dijana Townsend ◽  
Lara J. Herrero ◽  
Ali Zaid ◽  
Michael S. Rolph ◽  
...  

ABSTRACTHuman respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood.In vivostudies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin- and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin- and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load.IMPORTANCEThis study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity.


2006 ◽  
Vol 80 (1) ◽  
pp. 537-540 ◽  
Author(s):  
Xia-qing Li ◽  
Zhen F. Fu ◽  
Rene Alvarez ◽  
Christine Henderson ◽  
Ralph A. Tripp

ABSTRACT Respiratory syncytial virus (RSV) is a primary cause of morbidity and life-threatening lower respiratory tract disease in infants and young children. Children with acute RSV bronchiolitis often develop respiratory sequelae, but the disease mechanisms are poorly understood. Mounting evidence suggests that RSV may mediate persistent infection. Using immunohistochemistry to identify RSV and RSV-infected cell types, we show that RSV infects primary neurons and neuronal processes that innervate the lungs through a process that involves RSV G protein and the G protein CX3C motif. These findings suggest a mechanism for disease chronicity and have important implications for RSV disease intervention strategies.


PEDIATRICS ◽  
1987 ◽  
Vol 79 (3) ◽  
pp. 475-478
Author(s):  

Ribavirin is an antiviral drug that has recently been approved by the FDA in an aerosolized form for the therapy of respiratory syncytial virus infections in hospitalized children who do not require assisted ventilation. Ribavirin is different from other antiviral drugs both in its spectrum of activity and in its mode of administration.1,2 The following statement is presented to identify which children should be considered for ribavirin therapy. Questions also have arisen as to the benefits afforded by treatment in comparison to the potential unknown toxicity of the drug and as to whether ribavirin should be administered to infants who require assisted ventilation; the package insert has warned against using the drug in such patients. Whether pregnant women or personnel who care for infants being treated with ribavirin are at risk from exposure to the drug is also of concern. Finally, physicians must be aware that the cost of ribavirin needed for three days of therapy is almost $700. BACKGROUND Respiratory Syncytial Virus Disease Respiratory syncytial virus is the most important cause of lower respiratory tract disease in infants and young children. It usually appears in yearly winter to spring outbreaks and infects essentially all children during their first 3 years of life. The number of infected infants who require hospitalization has been estimated to range in different locations from one in 50 to one in 1,000. Currently, the mortality in hospitalized infants who were previously normal is low, less than 1%.3 In infants with underlying diseases, however, the mortality may be strikingly higher.3-5


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