Influenza Hemagglutinin and Neuraminidase Membrane Glycoproteins

Gamblin, Steven J.; Skehel, J.J.

doi:10.1074/jbc.r110.129809

Cited by 550 publications

(551 citation statements)

References 95 publications

(135 reference statements)

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“…Host cell attachment by IAV is mediated by the HA glycoprotein, which binds to specific types of Neu5Ac-containing receptors. 39 The towering structure of the MUC1 extracellular domain, estimated to be 200-500 nm in length when fully glycosylated, 21 plus expression of an abundance of terminally linked Neu5Ac is a likely first point of contact for HA binding by IAV that has penetrated the overlying gel mucus layer and gained access to the epithelial cell surface. Such chemoattraction and adherence to specific mucin carbohydrates have also been demonstrated for mouse adenovirus type I (MAVS-1) 40 and respiratory syncytial virus (RSV), 13 as well as bacteria including Campylobacter jejuni, 24 Helicobacter pylori 26 and Pseudomonas aeruginosa.…”

Section: Discussionmentioning

confidence: 99%

The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

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Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency. Utilizing human lung epithelial cells, we found that IAV associates with the cs-mucin MUC1 but not MUC13 or MUC16. Overexpression of MUC1 by epithelial cells or the addition of sialylated synthetic MUC1 constructs, reduced IAV infection in vitro. In addition, Muc1 À / À mice infected with IAV exhibited enhanced morbidity and mortality, as well as greater inflammatory mediator responses compared to wild type mice. This study implicates the cs-mucin MUC1 as a critical and dynamic component of the innate host response that limits the severity of influenza and provides the foundation for exploration of MUC1 in resolving inflammatory disease.

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Section: Discussionmentioning

confidence: 99%

The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

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“…Eleven conserved amino acids make contact with DANA (Figure 1) while another 6 conserved amino acids form a “second shell” 25 that holds the active site residues in place. The whole appears rather rigid, providing the basis of several drug design approaches (see reviews 2,6,26–30 .…”

Section: Neuraminidase Structural Domainsmentioning

confidence: 99%

Influenza neuraminidase

Air

2011

Influenza Resp Viruses

215

216

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Influenza neuraminidase is the target of two licensed antivirals that have been very successful, with several more in development. However, neuraminidase has been largely ignored as a vaccine target despite evidence that inclusion of neuraminidase in the subunit vaccine gives increased protection. This article describes current knowledge on the structure, enzyme activity and antigenic significance of neuraminidase.

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“…Influenza A viruses (IAVs) are classified into subtypes based on the antigenic differences of the surface glycoproteins haemagglutinin (HA) and neuraminidase (NA) into 18 HA and 11 NA subtypes, with aquatic birds considered the natural hosts of all subtypes of except H17N10 and H18N11 viruses (Fouchier et al, 2005;Gamblin & Skehel, 2010;Tong et al, 2012Tong et al, , 2013Webster et al, 1992). IAVs of the H9N2 subtype are low-pathogenic viruses, and two geographically distinct lineages have been described -the North American and Eurasian lineages.…”

Section: Introductionmentioning

confidence: 99%

Replication and transmission of mammalian-adapted H9 subtype influenza virus in pigs and quail

Obadan

Kimble

Rajão

et al. 2015

Journal of General Virology

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Influenza A virus is a major pathogen of birds, swine and humans. Strains can jump between species in a process often requiring mutations and reassortment, resulting in outbreaks and, potentially, pandemics. H9N2 avian influenza is predominant in poultry across Asia and occasionally infects humans and swine. Pandemic H1N1 (H1N1pdm) is endemic in humans and swine and has a history of reassortment in pigs. Previous studies have shown the compatibility of H9N2 and H1N1pdm for reassortment in ferrets, a model for human infection and transmission. Here, the effects of ferret adaptation of H9 surface gene segments on the infectivity and transmission in at-risk natural hosts, specifically swine and quail, were analysed. Reassortant H9N1 and H9N2 viruses, carrying seven or six gene segments from H1N1pdm, showed infectivity and transmissibility in swine, unlike the wholly avian H9N2 virus with ferretadapted surface genes. In quail, only the reassortant H9N2 with the six internal gene segments from the H1N1pdm strain was able to infect and transmit, although less efficiently than the wholly avian H9N2 virus with ferret-adapted surface genes. These results highlight that ferretadapted mutations on the haemagglutinin of H9 subtype virus do not restrict the ability of the virus to infect swine and quail, and that the ability to transmit in these species depends on the context of the whole virus. As such, this study emphasizes the threat that H9N2 reassortant viruses pose to humans and agricultural species and the importance of the genetic constellation of the virus to its ability to replicate and transmit in natural hosts of influenza.

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Influenza Hemagglutinin and Neuraminidase Membrane Glycoproteins

Cited by 550 publications

References 95 publications

The cell surface mucin MUC1 limits the severity of influenza A virus infection

The cell surface mucin MUC1 limits the severity of influenza A virus infection

Influenza neuraminidase

Replication and transmission of mammalian-adapted H9 subtype influenza virus in pigs and quail

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