tetano
Editor, Senior Moderator
Ann Am Thorac Soc. 2014 Mar 18. [Epub ahead of print]
Differential Responses to Rhinovirus and Influenza-associated Pulmonary Exacerbations in Patients with Cystic Fibrosis.
Ramirez IA1, Caverly LL, Kalikin LM, Goldsmith AM, Lewis TC, Burke DT, Lipuma JJ, Sajjan US, Hershenson MB.
Author information
Abstract
Rationale: The mechanism by which viruses cause exacerbations of chronic airways disease, and the capacity of cystic fibrosis (CF) patients to respond to viral infections, are not precisely known. Objectives: To determine the antiviral response to infection in patients with CF. Methods: Sputum and bronchoalveolar lavage fluid were collected from CF patients with respiratory exacerbation. Viruses were detected using a single-step multiplex polymerase chain reaction (PCR)-based assay and a multiplex PCR-ligase detection reaction assay. Gene expression of 84 antiviral response genes was measured using a focused quantitative PCR gene array. Measurements and Main Results: We examined 56 samples from 36 patients with respiratory exacerbation. Twenty-three samples tested virus-positive and 33 virus-negative. Five genes were upregulated at least 2-fold by viral infection (CXCL10, CXCL11, IL15, SUGT1, TLR8). When we compared exacerbations caused by rhinovirus (RV, n=12) and influenza (n=7) to virus-negative specimens, we found distinct patterns of antiviral gene expression. RV induced >2-fold expression of eight genes including CXCL10, CXCL11 and CCL5, genes encoding chemokines for mononuclear cells, as well as IFIH1, the gene encoding MDA-5, an RNA helicase recognizing RV double-stranded RNA. Influenza induced overexpression of 16 genes including CXCL8, IL1B and TNF, cytokines stimulating neutrophilic and systemic inflammation; MAP2K1, MAP3K7 and TBK1, kinases upstream of NF-κB activation; and MX1 and ISG15, interferon-stimulated genes involved in influenza resistance. Conclusions: We conclude that viral-induced exacerbations of CF are associated with immune responses tailored to specific infections. Influenza induced a more potent response consisting of inflammation and interferon-stimulated genes, whereas RV infection had a pronounced effect on chemokine expression. As far as we are aware, this study is the first to compare specific responses to different viruses in live patients with chronic airways disease.
PMID:
24641803
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24641803
Differential Responses to Rhinovirus and Influenza-associated Pulmonary Exacerbations in Patients with Cystic Fibrosis.
Ramirez IA1, Caverly LL, Kalikin LM, Goldsmith AM, Lewis TC, Burke DT, Lipuma JJ, Sajjan US, Hershenson MB.
Author information
Abstract
Rationale: The mechanism by which viruses cause exacerbations of chronic airways disease, and the capacity of cystic fibrosis (CF) patients to respond to viral infections, are not precisely known. Objectives: To determine the antiviral response to infection in patients with CF. Methods: Sputum and bronchoalveolar lavage fluid were collected from CF patients with respiratory exacerbation. Viruses were detected using a single-step multiplex polymerase chain reaction (PCR)-based assay and a multiplex PCR-ligase detection reaction assay. Gene expression of 84 antiviral response genes was measured using a focused quantitative PCR gene array. Measurements and Main Results: We examined 56 samples from 36 patients with respiratory exacerbation. Twenty-three samples tested virus-positive and 33 virus-negative. Five genes were upregulated at least 2-fold by viral infection (CXCL10, CXCL11, IL15, SUGT1, TLR8). When we compared exacerbations caused by rhinovirus (RV, n=12) and influenza (n=7) to virus-negative specimens, we found distinct patterns of antiviral gene expression. RV induced >2-fold expression of eight genes including CXCL10, CXCL11 and CCL5, genes encoding chemokines for mononuclear cells, as well as IFIH1, the gene encoding MDA-5, an RNA helicase recognizing RV double-stranded RNA. Influenza induced overexpression of 16 genes including CXCL8, IL1B and TNF, cytokines stimulating neutrophilic and systemic inflammation; MAP2K1, MAP3K7 and TBK1, kinases upstream of NF-κB activation; and MX1 and ISG15, interferon-stimulated genes involved in influenza resistance. Conclusions: We conclude that viral-induced exacerbations of CF are associated with immune responses tailored to specific infections. Influenza induced a more potent response consisting of inflammation and interferon-stimulated genes, whereas RV infection had a pronounced effect on chemokine expression. As far as we are aware, this study is the first to compare specific responses to different viruses in live patients with chronic airways disease.
PMID:
24641803
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24641803