Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated on gene expression profiling

• Published in: Pediatrics international Vol. 55; no. 5; pp. 572 - 577
• Main Authors: Yamashita, Nobuko, Tsukahara, Hirokazu, Tsuge, Mitsuru, Nagaoka, Yoshiharu, Yashiro, Masato, Saito, Yukie, Fujii, Yosuke, Oka, Takashi, Morishima, Tsuneo
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.10.2013
• Subjects: Alkaline phosphatase; Antibodies, Viral - immunology; central nervous system manifestations; Child; Child, Preschool; DNA, Viral - genetics; Female; Gene expression; gene expression profile; Gene Expression Profiling; Gene Expression Regulation; Humans; Immunity, Innate; Influenza; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - immunology; influenza A(H1N1)pdm09; Influenza, Human - genetics; Influenza, Human - immunology; Male; Microarray Analysis; Nervous system; Pathogenesis; Pediatrics; pneumonia; Retrospective Studies; central nervous system manifestations; gene expression profile; pneumonia; influenza A(H1N1)pdm09
• ISSN: 1328-8067; 1442-200X; 1442-200X
• DOI: 10.1111/ped.12139

Background The pathogenic mechanisms underlying influenza A(H1N1)pdm09‐associated central nervous system (CNS) manifestations and pneumonia remain unclear. This study examined A(H1N1)pdm09 host responses using gene expression profiles of patients’ peripheral blood. Methods Sixteen A(H1N1)pdm09‐infected children in three groups were examined: a CNS group, with convulsion and altered consciousness (n = 6); a pneumonia (Pneu) group (n = 5); and a group of infected control patients (n = 5). The signal ratios of the acute to recovery phases in CNS or Pneu were analyzed versus those of the control. Results The CNS (619 transcripts) and Pneu (656 transcripts) groups had significantly increased signal ratios compared to the control group. Regarding the increased ratios of transcripts shown by multiple probes, contactin‐associated protein‐like 3 transcripts, oleoyl‐ACP hydrolase transcripts, and interleukin 1 type 1 receptor were observed in CNS and Pneu. Increased ratios of prostaglandin‐endoperoxide synthase 2 and α‐synuclein were characteristic of CNS. Alkaline phosphatase and the Fc fragment of IgA receptor were characteristic of Pneu. Regarding enriched gene ontology terms, ‘response to lipopolysaccharide’, ‘innate immune response’, and ‘intrinsic to membrane’ were observed commonly in CNS and Pneu. Enriched gene ontology terms related to ‘hemoglobin’ and ‘hemostasis’ were, respectively, characteristic of CNS and Pneu. Conclusion These symptom‐associated transcripts might be some clues to the pathogenesis of the A(H1N1)pdm09 infection.