Dataset Information

Highly Sensitive in Vitro Diagnostic System of Pandemic Influenza A (H1N1) Virus Infection with Specific MicroRNA as a Biomarker.

ABSTRACT: Several microRNAs (miRNAs) have been reported to be closely related to influenza A virus infection, replication, and immune response. Therefore, the development of the infectious-disease detection system using miRNAs as biomarkers is actively underway. Herein, we identified two miRNAs (miR-181c-5p and miR-1254) as biomarkers for detection of pandemic influenza A H1N1 virus infection and proposed the catalytic hairpin assembly-based in vitro diagnostic (CIVD) system for a highly sensitive diagnosis; this system is composed of two sets of cascade hairpin probes enabling to detect miR-181c-5p and miR-1254. We demonstrated that CIVD kits could not only detect subnanomolar levels of target miRNAs but also distinguish even single-base mismatches. Moreover, this CIVD kit has shown excellent detection performance in real intracellular RNA samples and confirmed results similar to those of conventional methods (microarray and quantitative real-time polymerase chain reaction).

SUBMITTER: Lim J

PROVIDER: S-EPMC6740188 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Highly Sensitive in Vitro Diagnostic System of Pandemic Influenza A (H1N1) Virus Infection with Specific MicroRNA as a Biomarker.

Lim Jaewoo J Byun Jihyun J Guk Kyeonghye K Hwang Seul Gee SG Bae Pan Kee PK Jung Juyeon J Kang Taejoon T Lim Eun-Kyung EK

ACS omega 20190826 11

Several microRNAs (miRNAs) have been reported to be closely related to influenza A virus infection, replication, and immune response. Therefore, the development of the infectious-disease detection system using miRNAs as biomarkers is actively underway. Herein, we identified two miRNAs (miR-181c-5p and miR-1254) as biomarkers for detection of pandemic influenza A H1N1 virus infection and proposed the catalytic hairpin assembly-based in vitro diagnostic (CIVD) system for a highly sensitive diagnos ...[more]

PMID: 31528810

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Project description:The C-X-C motif chemokine ligand 17 (CXCL17) is chemotactic for myeloid cells, exhibits bactericidal activity, and exerts anti-viral functions. This chemokine is constitutively expressed in the respiratory tract, suggesting a role in lung defenses. However, little is known about the participation of CXCL17 against relevant respiratory pathogens in humans. Here, we evaluated the serum levels and lung tissue expression pattern of CXCL17 in a cohort of patients with severe pandemic influenza A(H1N1) from Mexico City. Peripheral blood samples obtained on admission and seven days after hospitalization were processed for determinations of serum CXCL17 levels by enzyme-linked immunosorbent assay (ELISA). The expression of CXCL17 was assessed by immunohistochemistry (IHQ) in lung autopsy specimens from patients that succumbed to the disease. Serum CXCL17 levels were also analyzed in two additional comparative cohorts of coronavirus disease 2019 (COVID-19) and pulmonary tuberculosis (TB) patients. Additionally, the expression of CXCL17 was tested in lung autopsy specimens from COVID-19 patients. A total of 122 patients were enrolled in the study, from which 68 had pandemic influenza A(H1N1), 24 had COVID-19, and 30 with PTB. CXCL17 was detected in post-mortem lung specimens from patients that died of pandemic influenza A(H1N1) and COVID-19. Interestingly, serum levels of CXCL17 were increased only in patients with pandemic influenza A(H1N1), but not COVID-19 and PTB. CXCL17 not only differentiated pandemic influenza A(H1N1) from other respiratory infections but showed prognostic value for influenza-associated mortality and renal failure in machine-learning algorithms and regression analyses. Using cell culture assays, we also identified that human alveolar A549 cells and peripheral blood monocyte-derived macrophages increase their CXCL17 production capacity after influenza A(H1N1) pdm09 virus infection. Our results for the first time demonstrate an induction of CXCL17 specifically during pandemic influenza A(H1N1), but not COVID-19 and PTB in humans. These findings could be of great utility to differentiate influenza and COVID-19 and to predict poor prognosis specially at settings of high incidence of pandemic A(H1N1). Future studies on the role of CXCL17 not only in severe pandemic influenza, but also in seasonal influenza, COVID-19, and PTB are required to validate our results.

Project description:MicroRNAs have been implicated in the regulation of gene expression of various biological processes in a post-transcriptional manner under physiological and pathological conditions including host responses to viral infections. The 2009 pandemic H1N1 influenza virus is an emerging reassortant strain of swine, human and bird influenza virus that can cause mild to severe illness and even death. To further understand the molecular pathogenesis of the 2009 pandemic H1N1 influenza virus, we profiled cellular microRNAs of lungs from BALB/c mice infected with wild-type 2009 pandemic influenza virus A/Beijing/501/2009 (H1N1) (hereafter referred to as BJ501) and mouse-adapted influenza virus A/Puerto Rico/8/1934 (H1N1) (hereafter referred to as PR8) for comparison. Microarray analysis showed both the influenza virus BJ501 and PR8 infection induced strain- and temporal-specific microRNA expression patterns and that their infection caused a group of common and distinct differentially expressed microRNAs. Characteristically, more differentially expressed microRNAs were aroused on day 5 post infection than on day 2 and more up-regulated differentially expressed microRNAs were provoked than the down-regulated for both strains of influenza virus. Finally, 47 differentially expressed microRNAs were obtained for the infection of both strains of H1N1 influenza virus with 29 for influenza virus BJ501 and 43 for PR8. Among them, 15 microRNAs had no reported function, while 32 including miR-155 and miR-233 are known to play important roles in cancer, immunity and antiviral activity. Pathway enrichment analyses of the predicted targets revealed that the transforming growth factor-? (TGF-?) signaling pathway was the key cellular pathway associated with the differentially expressed miRNAs during influenza virus PR8 or BJ501 infection. To our knowledge, this is the first report of microRNA expression profiles of the 2009 pandemic H1N1 influenza virus in a mouse model, and our findings might offer novel therapy targets for influenza virus infection.

Dataset Information

Highly Sensitive in Vitro Diagnostic System of Pandemic Influenza A (H1N1) Virus Infection with Specific MicroRNA as a Biomarker.

Publications

Highly Sensitive in Vitro Diagnostic System of Pandemic Influenza A (H1N1) Virus Infection with Specific MicroRNA as a Biomarker.

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