title: Streptococcus pneumoniae Enhances Human Respiratory Syncytial Virus Infection In Vitro and In Vivo.
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.
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: D Tien
authors.initials: DT
authors.lastname: Nguyen
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Rogier
authors.initials: R
authors.lastname: Louwen
authors.affiliation: National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
authors.forename: Karin
authors.initials: K
authors.lastname: Elberse
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: van Amerongen
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Selma
authors.initials: S
authors.lastname: Yüksel
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Ad
authors.initials: A
authors.lastname: Luijendijk
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Albert D M E
authors.initials: AD
authors.lastname: Osterhaus
authors.affiliation: Department of Microbiology, Boston University School of Medicine, Boston, MA, United States of America.
authors.forename: W Paul
authors.initials: WP
authors.lastname: Duprex
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Rik L
authors.initials: RL
authors.lastname: de Swart
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000502:physiology; D002460:Cell Line; D060085:Coinfection / Q000382:microbiology*; D005260:Female; D006801:Humans; D056265:Microbial Interactions; D009300:Nasal Septum / Q000382:microbiology; D009439:Neuraminidase / Q000502:physiology; D011008:Pneumococcal Infections / Q000821:virology*; D018357:Respiratory Syncytial Virus Infections / Q000382:microbiology*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D016205:Sigmodontinae; D013296:Streptococcus pneumoniae / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D009439:Neuraminidase