Influenza virus receptors in the human airway

Shinya, Kyoko; Ebina, Masahito; Yamada, S.; Ono, Masao; Kasai, Noriyuki; Kawaoka, Yoshihiro

doi:10.1038/440435a

Cited by 1,256 publications

(1,154 citation statements)

References 7 publications

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“…The avian influenza virus preferentially binds to SAa2-3Gal, which is expressed in distal bronchioles and type II pneumocytes in the lower respiratory tract. 31 It was shown in vitro that the 2009 H1N1 virus binds to both SAa2-6Gal and SAa2-3Gal. 32 In this study, cases 1-4 presented with DAD with InfA-NP-positive pneumocytes.…”

Section: Discussionmentioning

confidence: 99%

Histopathological and immunohistochemical findings of 20 autopsy cases with 2009 H1N1 virus infection

et al. 2012

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, were histopathologically analyzed. Hematoxylin-eosin staining, immunohistochemistry for type A influenza nucleoprotein antigen, and real-time reverse transcription-PCR assay for viral RNA were performed on formalin-fixed and paraffin-embedded specimens. In addition, the D222G amino acid substitution in influenza virus hemagglutinin, which binds to specific cell receptors, was analyzed in formalinfixed and paraffin-embedded trachea and lung sections by direct sequencing of PCR-amplified products. There were several histopathological patterns in the lung according to the most remarkable findings in each case: acute diffuse alveolar damage (DAD) with a hyaline membrane (four cases), organized DAD (one case), acute massive intra-alveolar edema with variable degrees of hemorrhage (three cases), neutrophilic bronchopneumonia (five cases) and tracheobronchitis with limited histopathological changes in alveoli (four cases). In two cases, the main findings were due to preexisting disease. Influenza virus antigen was only detected in the respiratory tract in 10 cases by immunohistochemistry. The antigen was detected in type II pneumocytes (three cases) in the epithelial cells of the trachea, bronchi and glands (six cases), and in the epithelial cells in both of the above (one case). The four cases with acute DAD presented with antigen-positive type II pneumocytes. In one case, the D222G substitution was detected in the lung as a major sequence, although 222D was prominent in the trachea, suggesting that selection of the viral clones occurred in the respiratory tract. In five

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Section: Discussionmentioning

confidence: 99%

Histopathological and immunohistochemical findings of 20 autopsy cases with 2009 H1N1 virus infection

et al. 2012

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“…The mouse lung differs from humans not only in the types of (viral) receptors expressed, but also their distribution within lung compartments. Alpha-2,6 sialic acid-linked receptors, for example, are expressed in the more distal parenchyma of the lung in mice but more proximally, in the trachea, in humans; while the reverse is true for alpha-2,3 sialic acid-linked receptors [46,47]. Receptor expression also differs with regards to the location on the cell membrane.…”

Section: A Brief History Of In-vivo Gene Therapymentioning

confidence: 99%

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Haasteren

Hyde

Gill

2018

Expert Opinion on Biological Therapy

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Introduction: Ex-vivo gene therapy has had significant clinical impact over the last couple of years and in-vivo gene therapy products are being approved for clinical use. Gene therapy and gene editing approaches have huge potential to treat genetic disease and chronic illness. Areas covered: This article provides a review of in-vivo approaches for gene therapy in the lung and liver, exploiting non-viral and viral vectors with varying serotypes and pseudotypes to target-specific cells. Antibody responses inhibiting viral vectors continue to constrain effective repeat administration. Lessons learned from ex-vivo gene therapy and genome editing are also discussed. Expert opinion: The fields of lung and liver in-vivo gene therapy are thriving and a comparison highlights obstacles and opportunities for both. Overcoming immunological issues associated with repeated administration of viral vectors remains a key challenge. The addition of targeted small molecules in combination with viral vectors may offer one solution. A substantial bottleneck to the widespread adoption of in-vivo gene therapy is how to ensure sufficient capacity for clinical-grade vector production. In the future, the exploitation of gene editing approaches for in-vivo disease treatment may facilitate the resurgence of non-viral gene transfer approaches, which tend to be eclipsed by more efficient viral vectors.

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“…It is noteworthy that mouse strain-dependent differences in the sialic acid composition have been reported [79]. Importantly, human and mouse airways differ in their pulmonary sialic acid repertoire [80,81] and the pneumococcus has evolved to specifically sense and respond to human sialic composition [82]. Therefore, the role of neuraminidases in human pneumonia is potentially underestimated by extrapolating from mouse models.…”

Section: Discussionmentioning

confidence: 99%

Assessing the function of pneumococcal neuraminidases NanA, NanB and NanC inin vitroandin vivolung infection models using monoclonal antibodies

et al. 2018

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Streptococcus pneumoniae isolates express up to three neuraminidases (sialidases), NanA, NanB and NanC, all of which cleave the terminal sialic acid of glycan-structures that decorate host cell surfaces. Most research has focused on the role of NanA with limited investigations evaluating the roles of all three neuraminidases in host-pathogen interactions. We generated two highly potent monoclonal antibodies (mAbs), one that blocks the enzymatic activity of NanA and one cross-neutralizing NanB and NanC. Total neuraminidase activity of clinical S. pneumoniae isolates could be inhibited by this mAb combination in enzymatic assays. To detect desialylation of cell surfaces by pneumococcal neuraminidases, primary human tracheal/bronchial mucocilial epithelial tissues were infected with S. pneumoniae and stained with peanut lectin. Simultaneous targeting of the neuraminidases was required to prevent desialylation, suggesting that inhibition of NanA alone is not sufficient to preserve terminal lung glycans. Importantly, we also found that all three neuraminidases increased the interaction of S. pneumoniae with human airway epithelial cells. Lectin-staining of lung tissues of mice pre-treated with mAbs before intranasal challenge with S. pneumoniae confirmed that both anti-NanA and anti-NanBC mAbs were required to effectively block desialylation of the respiratory epithelium in vivo. Despite this, no effect on survival, reduction in pulmonary bacterial load, or significant changes in cytokine responses were observed. This suggests that neuraminidases have no pivotal role in this murine pneumonia model that is induced by high bacterial challenge inocula and does not progress from colonization as it happens in the human host.

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Influenza virus receptors in the human airway

Cited by 1,256 publications

References 7 publications

Histopathological and immunohistochemical findings of 20 autopsy cases with 2009 H1N1 virus infection

Histopathological and immunohistochemical findings of 20 autopsy cases with 2009 H1N1 virus infection

Lessons learned from lung and liver in-vivo gene therapy: implications for the future

Assessing the function of pneumococcal neuraminidases NanA, NanB and NanC inin vitroandin vivolung infection models using monoclonal antibodies

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