Nasopharyngeal gene expression, a novel approach to study the course of respiratory syncytial virus infection

Respiratory syncytial virus (RSV) causes mild infections in the vast majority of children. However, in some cases, it causes severe disease, such as bronchiolitis and pneumonia. Development of severe RSV infection is determined by the host response. Therefore, the main aim of this study was to identify biomarkers associated with severe RSV infection. To identify biomarkers, nasopharyngeal gene expression was profiled by microarray studies, resulting in the selection of five genes: ubiquitin D, tetraspanin 8, mucin 13, β-microseminoprotein and chemokine ligand 7. These genes were validated by real-time quantitative PCR in an independent validation cohort, which confirmed significant differences in gene expression between mildly and severely infected and between recovery and acute patients. Nasopharyngeal aspirate samples are regularly taken when a viral respiratory tract infection is suspected. In this article, we describe a method to discriminate between mild and severe RSV infection based on differential host gene expression. The combination of pathogen detection and host gene expression analysis in nasopharyngeal aspirates will significantly improve the diagnosis and prognosis of respiratory tract infections

Short-term repeated HRV-16 exposure results in an attenuated immune response <i>in vivo</i> in humans - Fig 5

<p>Plasma IP-10 levels following placebo inoculation and HRV challenge (panel A) and following two HRV challenges separated by one week time (panel B). Panel C shows the peak levels in the first four days post-challenge in the group that received placebo, followed by a HRV challenge (bar 1 and 2) and in the group that were challenged with HRV twice (bar 3 and 4). Data are represented as geometric mean and 95% CI. Lower detection limit was 156 pg/mL.</p

Short-term repeated HRV-16 exposure results in an attenuated immune response <i>in vivo</i> in humans

<div><p>Introduction</p><p>Naturally, development of adaptive immunity following HRV infection affects the immune response. However, it is currently unclear whether or not HRV re-exposure within a short time frame leads to an altered innate immune response. The “experimental cold model” is used to investigate the pathogenesis of HRV infection and allows us to investigate the effects of repeated exposure on both local and systemic innate immunity.</p><p>Methods</p><p>40 healthy male and female (1:1) subjects were nasally inoculated with HRV-16 or placebo. One week later, all subjects received HRV-16. Baseline seronegative subjects (n = 18) were included for further analysis.</p><p>Results</p><p>Infection rate was 82%. Primary HRV infection induced a marked increase in viral load and IP-10 levels in nasal wash, while a similar trend was observed for IL-6 and IL-10. Apart from an increase in IP-10 plasma levels, HRV infection did not induce systemic immune effects nor lower respiratory tract inflammation. With similar viral load present during the second HRV challenge, IP-10 and IL-6 in nasal wash showed no increase, but gradually declined, with a similar trend for IL-10.</p><p>Conclusion</p><p>Upon a second HRV challenge one week after the first, a less pronounced response for several innate immune parameters is observed. This could be the result of immunological tolerance and possibly increases vulnerability towards secondary infections.</p></div

Experimental design of the study.

<p>Experimental design of the study.</p

Demographic characteristics of the 18 seronegative subjects who displayed positive infection that were included in the final analysis.

<p>Parameters were assessed during the screening visit. M: male, F: female. BMI: body mass index. Data are presented as medians [interquartile range].</p

Short-term repeated HRV-16 exposure results in an attenuated immune response <i>in vivo</i> in humans - Fig 3

<p>Viral load levels in nasal wash following placebo inoculation and HRV challenge (panel A) and following two HRV challenges separated by one week time (panel B). Panel C shows the peak levels in the first four days post-challenge in the group that received placebo, followed by a HRV challenge (bars 1 and 2), and in the group that were challenged with HRV twice (bars 3 and 4). Data are represented as geometric mean and 95% CI.</p