期刊
CLINICAL MICROBIOLOGY AND INFECTION
卷 19, 期 7, 页码 668-673出版社
ELSEVIER SCI LTD
DOI: 10.1111/j.1469-0691.2012.03984.x
关键词
D222 variants; haemagglutinin; influenza; polymorphisms; ultra-deep pyrosequencing
资金
- Italian Ministry of Health
- Istituto Superiore di Sanita
- Regione Lombardia
- European Union [278433-PREDEMICS]
- Fondazione Cariplo [2011]
This study was aimed at establishing the genetic heterogeneity of influenza virus haemagglutinin (HA) gene quasi-species and the polymorphisms at codon222, by application of ultra-deep pyrosequencing (UDPS) to respiratory samples from patients hospitalized for influenzaA(H1N1)pdm09 infection, presenting with severe or moderate-mild disease. HA diversity was significantly higher in samples collected from patients with severe manifestations than in those from patients with moderate-mild manifestations (p0.02). D222 polymorphism was detected in 40.7% of patients by UDPS, and in only 7.1% by Sanger sequencing. D222E, D222G, D222N and D222A were observed in 37.0%, 11.1%, 7.4% and 3.7% of patients, respectively; 10.7% of samples harboured more than two variants. The relative frequency of each single variant showed a wide range of intrapatient variation. D222G/N/A were detected, as either minor or predominant variants, only in severe cases, whereas D222E was equally represented in severe and moderate-mild infections. Other amino acid variants were observed at different positions within the analysed HA fragment. Consistent with higher heterogeneity, non-D222 variants were more frequently detected in severe cases than in moderate-mild cases. In addition, seven non-D222 mutations carried by minority variants, not previously described, were observed.
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