Limits...
Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In Vitro and In Vivo.

Nguyen DT, Louwen R, Elberse K, van Amerongen G, Yüksel S, Luijendijk A, Osterhaus AD, Duprex WP, de Swart RL - PLoS ONE (2015)

Bottom Line: Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo.However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact.These results demonstrate that pneumococcal colonization can enhance subsequent HRSV infection, and provide tools for additional mechanistic and intervention studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.

ABSTRACT
Human respiratory syncytial virus (HRSV) and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. It has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. However, studies on the influence of bacterial colonization of the upper respiratory tract on the pathogenesis of subsequent respiratory virus infections are scarce. Here, we have investigated whether pneumococcal colonization enhances subsequent HRSV infection. We used a newly generated recombinant subgroup B HRSV strain that expresses enhanced green fluorescent protein and pneumococcal isolates obtained from healthy children in disease-relevant in vitro and in vivo model systems. Three pneumococcal strains specifically enhanced in vitro HRSV infection of primary well-differentiated normal human bronchial epithelial cells grown at air-liquid interface, whereas two other strains did not. Since previous studies reported that bacterial neuraminidase enhanced HRSV infection in vitro, we measured pneumococcal neuraminidase activity in these cultures but found no correlation with the observed infection enhancement in our model. Subsequently, a selection of pneumococcal strains was used to induce nasal colonization of cotton rats, the best available small animal model for HRSV. Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was also associated with enhanced syncytium formation in vivo. However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact. These results demonstrate that pneumococcal colonization can enhance subsequent HRSV infection, and provide tools for additional mechanistic and intervention studies.

No MeSH data available.


Related in: MedlinePlus

HRSV infection in nasal septum of a S. pneumoniae colonized cotton rat.Composite microscopic UV images of the complete nasal septum of a cotton rat 5 d.p.i. showing a representative syncytium in the middle (scale bar represents 500 μm). The inset is a confocal laser scanning image of the same nasal septum with nuclei stained with TO-PRO3 (red; scale bar represents 100 μm).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4430531&req=5

pone.0127098.g003: HRSV infection in nasal septum of a S. pneumoniae colonized cotton rat.Composite microscopic UV images of the complete nasal septum of a cotton rat 5 d.p.i. showing a representative syncytium in the middle (scale bar represents 500 μm). The inset is a confocal laser scanning image of the same nasal septum with nuclei stained with TO-PRO3 (red; scale bar represents 100 μm).

Mentions: Upon necropsy, EGFP+ cells were detected in the nasal septum and conchae of all animals. No differences in numbers of EGFP+ cells were observed between the different groups, although absolute enumeration of these cells was impossible. Syncytia were observed in the nasal septum and conchae in 5 out of 6 animals of the group inoculated with S. pneumoniae strain 19F as compared to 1 out of 6 animals of the mock group (p<0.05, Fig 3). In the groups that had received S. pneumoniae strains 8, 15A or 23F these were seen in 1, 1 and 3 animals, respectively (not significantly different from the mock control). A small number of EGFP+ cells was found in the lungs in two animals that had received S. pneumoniae 19F or 23F (data not shown).


Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In Vitro and In Vivo.

Nguyen DT, Louwen R, Elberse K, van Amerongen G, Yüksel S, Luijendijk A, Osterhaus AD, Duprex WP, de Swart RL - PLoS ONE (2015)

HRSV infection in nasal septum of a S. pneumoniae colonized cotton rat.Composite microscopic UV images of the complete nasal septum of a cotton rat 5 d.p.i. showing a representative syncytium in the middle (scale bar represents 500 μm). The inset is a confocal laser scanning image of the same nasal septum with nuclei stained with TO-PRO3 (red; scale bar represents 100 μm).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430531&req=5

pone.0127098.g003: HRSV infection in nasal septum of a S. pneumoniae colonized cotton rat.Composite microscopic UV images of the complete nasal septum of a cotton rat 5 d.p.i. showing a representative syncytium in the middle (scale bar represents 500 μm). The inset is a confocal laser scanning image of the same nasal septum with nuclei stained with TO-PRO3 (red; scale bar represents 100 μm).
Mentions: Upon necropsy, EGFP+ cells were detected in the nasal septum and conchae of all animals. No differences in numbers of EGFP+ cells were observed between the different groups, although absolute enumeration of these cells was impossible. Syncytia were observed in the nasal septum and conchae in 5 out of 6 animals of the group inoculated with S. pneumoniae strain 19F as compared to 1 out of 6 animals of the mock group (p<0.05, Fig 3). In the groups that had received S. pneumoniae strains 8, 15A or 23F these were seen in 1, 1 and 3 animals, respectively (not significantly different from the mock control). A small number of EGFP+ cells was found in the lungs in two animals that had received S. pneumoniae 19F or 23F (data not shown).

Bottom Line: Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo.However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact.These results demonstrate that pneumococcal colonization can enhance subsequent HRSV infection, and provide tools for additional mechanistic and intervention studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.

ABSTRACT
Human respiratory syncytial virus (HRSV) and Streptococcus pneumoniae are important causative agents of respiratory tract infections. Both pathogens are associated with seasonal disease outbreaks in the pediatric population, and can often be detected simultaneously in infants hospitalized with bronchiolitis or pneumonia. It has been described that respiratory virus infections may predispose for bacterial superinfections, resulting in severe disease. However, studies on the influence of bacterial colonization of the upper respiratory tract on the pathogenesis of subsequent respiratory virus infections are scarce. Here, we have investigated whether pneumococcal colonization enhances subsequent HRSV infection. We used a newly generated recombinant subgroup B HRSV strain that expresses enhanced green fluorescent protein and pneumococcal isolates obtained from healthy children in disease-relevant in vitro and in vivo model systems. Three pneumococcal strains specifically enhanced in vitro HRSV infection of primary well-differentiated normal human bronchial epithelial cells grown at air-liquid interface, whereas two other strains did not. Since previous studies reported that bacterial neuraminidase enhanced HRSV infection in vitro, we measured pneumococcal neuraminidase activity in these cultures but found no correlation with the observed infection enhancement in our model. Subsequently, a selection of pneumococcal strains was used to induce nasal colonization of cotton rats, the best available small animal model for HRSV. Intranasal HRSV infection three days later resulted in strain-specific enhancement of HRSV replication in vivo. One S. pneumoniae strain enhanced HRSV both in vitro and in vivo, and was also associated with enhanced syncytium formation in vivo. However, neither pneumococci nor HRSV were found to spread from the upper to the lower respiratory tract, and neither pathogen was transmitted to naive cage mates by direct contact. These results demonstrate that pneumococcal colonization can enhance subsequent HRSV infection, and provide tools for additional mechanistic and intervention studies.

No MeSH data available.


Related in: MedlinePlus