The immune response to respiratory syncytial virus (RSV) infection has fascinated and frustrated investigators for decades. After adverse responses to early attempts at vaccination, it became popularly held that disease following infection was related to overly aggressive immune responses. However, recent data illustrate that severe forms of disease are related to inadequate, rather than hyperresponsive, adaptive immune reactions. Thus, recovery from primary (and perhaps later) RSV infection is dependent on the quality of innate immune responses. These findings should have enormous significance to the development of vaccines and antiviral compounds.
[Show abstract][Hide abstract] ABSTRACT: To determine the burden of norovirus infections in children stools from a longitudinal community cohort were evaluated using reverse transcription polymerase chain reaction. Norovirus was detected in 21.3% of diarrheal and 8.0% of nondiarrheal stools (P < 0.01). Norovirus diarrhea was highly associated with age and the odds ratio for norovirus diarrhea fell by 2.8% per month (OR = 0.97, 95% CI: 0.95-0.99). Norovirus seems to be an important etiology of community acquired diarrhea in this study population.
[Show abstract][Hide abstract] ABSTRACT: Previously healthy children hospitalized with respiratory syncytial virus (RSV) received motavizumab (3, 15, or 30 mg/kg intravenously), an RSV-specific monoclonal antibody, or placebo. Safety, tolerability, motavizumab concentrations, and immunogenicity were assessed. Cultivatable RSV in the upper respiratory tract was significantly reduced with motavizumab compared with placebo day 1 post-treatment. No adverse events were considered motavizumab-related by site investigators.
[Show abstract][Hide abstract] ABSTRACT: Respiratory syncytial virus (RSV) is a common respiratory viral infection in children which is associated with immune dysregulation and subsequent induction and exacerbations of asthma. We recently reported that treatment of primary human epithelial cells (PHBE cells) with transforming growth factor beta (TGF-beta) enhanced RSV replication. Here, we report that the enhancement of RSV replication is mediated by induction of cell cycle arrest. These data were confirmed by using pharmacologic inhibitors of cell cycle progression, which significantly enhanced RSV replication. Our data also showed that RSV infection alone resulted in cell cycle arrest in A549 and PHBE cells. Interestingly, our data showed that RSV infection induced the expression of TGF-beta in epithelial cells. Blocking of TGF-beta with anti-TGF-beta antibody or use of a specific TGF-beta receptor signaling inhibitor resulted in rescue of the RSV-induced cell cycle arrest, suggesting an autocrine mechanism. Collectively, our data demonstrate that RSV regulates the cell cycle through TGF-beta in order to enhance its replication. These findings identify a novel pathway for upregulation of virus replication and suggest a plausible mechanism for association of RSV with immune dysregulation and asthma.
Journal of Virology 09/2009; 83(23):12424-31. DOI:10.1128/JVI.00806-09 · 4.44 Impact Factor
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