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Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus.

ABSTRACT: Mutations in the receptor-binding site of the hemagglutinin of pandemic influenza A(H1N1) 2009 viruses have been detected sporadically. An Asp222Gly (D222G) substitution has been associated with severe or fatal disease. Here we show that 222G variants infected a higher proportion of ciliated cells in cultures of human airway epithelium than did viruses with 222D or 222E, which targeted mainly nonciliated cells. Carbohydrate microarray analyses showed that 222G variants bind a broader range of α2-3-linked sialyl receptor sequences of a type expressed on ciliated bronchial epithelial cells and on epithelia within the lung. These features of 222G mutants may contribute to exacerbation of disease.

SUBMITTER: Liu Y

PROVIDER: S-EPMC2977873 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus.

Liu Yan Y Childs Robert A RA Matrosovich Tatyana T Wharton Stephen S Palma Angelina S AS Chai Wengang W Daniels Rodney R Gregory Victoria V Uhlendorff Jennifer J Kiso Makoto M Klenk Hans-Dieter HD Hay Alan A Feizi Ten T Matrosovich Mikhail M

Journal of virology 20100908 22

Mutations in the receptor-binding site of the hemagglutinin of pandemic influenza A(H1N1) 2009 viruses have been detected sporadically. An Asp222Gly (D222G) substitution has been associated with severe or fatal disease. Here we show that 222G variants infected a higher proportion of ciliated cells in cultures of human airway epithelium than did viruses with 222D or 222E, which targeted mainly nonciliated cells. Carbohydrate microarray analyses showed that 222G variants bind a broader range of α2 ...[more]

PMID: 20826688

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Project description:BackgroundFollowing the emergence of 2009 pandemic influenza A virus subtype H1N1 (A[H1N1]pdm09) in the United States and Mexico in April 2009, A(H1N1)pdm09 spread rapidly all over the world. There is a dearth of information about the epidemiology of A(H1N1)pdm09 in Africa, including Morocco. We describe the epidemiologic characteristics of the A(H1N1)pdm09 epidemic in Morocco during 2009-2010, including transmissibility and risk factors associated with fatal disease.MethodsWe implemented influenza surveillance for patients presenting with influenza-like illness (ILI) at 136 private and public clinics for patients with severe acute respiratory illness (SARI) at 16 regional public hospitals from June 2009 through February 2010. Respiratory samples and structured questionnaires were collected from all enrolled patients, and samples were tested by real-time reverse-transcription polymerase chain reaction for influenza viruses. We estimated the risk factors associated with fatal disease as well as the basic reproduction number (R(0)) and the serial interval of the pandemic virus.ResultsFrom June 2009 through February 2010, we obtained 3937 specimens, of which 1452 tested positive for influenza virus. Of these, 1398 (96%) were A(H1N1)pdm09. Forty percent of specimens from ILI cases (1056 of 2646) and 27% from SARI cases (342 of 1291) were positive for A(H1N1)pdm09. Sixty-four deaths occurred among laboratory-confirmed A(H1N1)pdm09 SARI cases. Among these cases, those who had hypertension (age-adjusted odd ratio [aOR], 28.2; 95% confidence interval [CI], 2.0-398.7), had neurological disorders (aOR, 7.5; 95% CI, 1.5-36.4), or were obese (aOR, 7.1; 95% CI, 1.6-31.1), as well as women of gestational age who were pregnant (aOR, 2.5; 95% CI, 1.1-5.6), were at increased risk of death. Across the country, elevated numbers of locally acquired infections were detected 4 months after the detection of the first laboratory-confirmed case and coincided with the expected influenza season (October-January) in Morocco. We obtained an R(0) estimate of 1.44 (95% CI, 1.32-1.56) and a mean serial interval (±SD) of 2.3 ± 1.4 days (95% CI, 1.6-3.0).ConclusionWidespread but delayed community transmission of A(H1N1)pdm09 occurred in Morocco in 2009, and A(H1N1)pdm09 became the dominant influenza virus subtype during the 2009-2010 influenza season. The transmissibility characteristics were similar to those observed in other countries.

Dataset Information

Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus.

Publications

Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus.

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