Influenza virus N-linked glycosylation and innate immunity

York, Ian A.; Stevens, James; Alymova, Irina V.

doi:10.1042/bsr20171505

Cited by 54 publications

(49 citation statements)

References 177 publications

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“…Protein glycosylation data presented here, including the coexistence of related protein glycoforms evidenced in this work, should be considered for designing antibody-based diagnostic tests targeting M. tuberculosis antigens. Besides, as reported for other pathogens [74,75], protein glycosylation diversity could be a key mechanism to provide antigenic variability aiding in the immune subversion of this pathogen.…”

Section: Resultsmentioning

confidence: 68%

Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate

et al. 2020

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Despite being the subject of intensive research, tuberculosis, caused by Mycobacterium tuberculosis, remains at present the leading cause of death from an infectious agent. Secreted and cell wall proteins interact with the host and play important roles in pathogenicity. These proteins are explored as candidate diagnostic markers, potential drug targets or vaccine antigens, and more recently special attention is being given to the role of their post-translational modifications. With the purpose of contributing to the proteomic and glycoproteomic characterization of this important pathogen, we performed a shotgun analysis of culture filtrate proteins of M. tuberculosis based on a liquid nano-HPLC tandem mass spectrometry and a labelfree spectral counting normalization approach for protein quantification. We identified 1314 M. tuberculosis proteins in culture filtrate and found that the most abundant proteins belong to the extracellular region or cell wall compartment, and that the functional categories with higher protein abundance factor were virulence, detoxification and adaptation, and cell wall and cell processes. We could identify a group of proteins consistently detected in previous studies, most of which were highly abundant proteins. In culture filtrate, 140 proteins were predicted to contain one of the three types of bacterial N-terminal signal peptides. Besides, various proteins belonging to the ESX secretion systems, and to the PE and PPE families, secreted by the type VII secretion system using nonclassical secretion signals, were also identified. O-glycosylation was identified in 46 proteins, many of them lipoproteins and cell wall associated proteins. Finally, we provide proteomic evidence for 33 novel O-glycosylated proteins, aiding to the glycoproteomic characterization of relevant antigenic membrane and exported proteins. These findings are expected to collaborate with the research on pathogen derived biomarkers, virulence factors and vaccine candidates, and to provide clues to the understanding of the pathogenesis and survival strategies adopted by M. tuberculosis.

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Section: Resultsmentioning

confidence: 68%

Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate

et al. 2020

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“…The presence of multiple glycosites and the variation in the composition of the glycans at a glycosite, can result in a staggering number of permutations of protein glycoforms. Although the particular structure of the glycans at the glycosites may not impact protein immunogenicity, as reported in the case of hepatitis C virus 19 , the location and number or density of glycosites can have a profound impact on the innate immune response to virus 23 and on the antigenicity of viral envelope proteins 24,25 , as observed in the case of influenza A. Lastly, to further complicate our understanding of the effect of glycosylation on protein antigenicity, glycans display large internal motions that prevents their accurate description by any single 3D shape, in contrast to proteins 26,27 .…”

Section: Resultsmentioning

confidence: 99%

“…That the precise composition of the glycans may not alter antigenicity, suggests that glycan microheterogeneity may not heavily impact the exposed surface area of the protein. Nevertheless, such glycan variations have been shown to impact the ability of innate immune lectins, such as surfactant protein-D (SPD), to respond to the antigen 16,23 . Because SPD requires a cluster of high mannose glycans on the pathogenic protein in order to bind 16 , variations in the glycan composition can impair such a response.…”

Section: Resultsmentioning

confidence: 99%

Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

Grant

Montgomery

Ito

et al. 2020

Preprint

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Here we have generated 3D structures of glycoforms of the spike (S) protein SARS-CoV-2, based on reported 3D structures for the S protein and on reported glycomics data for the protein produced in HEK293 cells. We also report structures for glycoforms that represent those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi and ER), as well as those that are commonly observed on antigens present in other viruses.These models were subjected to MD simulation to take into account protein and glycan plasticity, and to determine the extent to which glycan microheterogeneity impacts antigenicity. Lastly, we have identified peptides in the S protein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the adaptive immune response to the SARS-CoV-2 virus or to a related vaccine.

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“…Protein glycosylation data presented here, including the coexistence of related protein glycoforms evidenced in this work, should be considered for designing antibody-based diagnostic test targeting M. tuberculosis antigens. Besides, as reported for other pathogens [68,69], protein glycosylation diversity could be a key mechanism to provide antigenic variability aiding in the immune subversion of this pathogen.…”

Section: Resultsmentioning

confidence: 78%

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

Tucci

Portela

Chetto³

et al. 2019

Preprint

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21 Despite being the subject of intensive research, tuberculosis, caused by Mycobacterium 22 tuberculosis, remains at present the leading cause of death from an infectious agent. Secreted 23 and cell wall proteins interact with the host and play important roles in pathogenicity. These 24 proteins have been explored as candidate diagnostic markers, potential drug targets or vaccine 25 antigens, and special attention has been given to the role of their post-translational 26 modifications. With the purpose of contributing to the proteomic characterization of this 27 important pathogen including an O-glycosylation profile analysis, we performed a shotgun 28 analysis of culture filtrate proteins of M. tuberculosis based on a liquid nano-HPLC tandem mass 29 spectrometry and a label-free spectral counting normalization approach for protein 30 quantification. We identified 1314 M. tuberculosis proteins in culture filtrate and found that the 31 most abundant proteins belong to the extracellular region or cell wall compartment, and that 32 the functional categories with higher protein abundance factor were virulence, detoxification 33 and adaptation, and cell wall and cell processes. In culture filtrate, 140 proteins were predicted 34 to contain one of the three types of bacterial N-terminal signal peptides. Besides, various 35 proteins belonging to the ESX secretion systems, and to the PE and PPE families, secreted by the 36 type VII secretion system using nonclassical secretion signals, were also identified. O-37 glycosylation was identified as a frequent modification, being present in 108 proteins, principally 38 lipoproteins and secreted immunogenic antigens. We could identify a group of proteins 39 consistently detected in previous studies, most of which were highly abundant proteins. 40 Interestingly, we also provide proteomic evidence for 62 novel O-glycosylated proteins, aiding 41 to the glycoproteomic characterization of relevant antigenic membrane and exported proteins. 48 HIV-positive people [1]. Although TB diagnosis and successful treatment averts millions of 49 deaths each year, there are still large and persistent gaps related to this infection that must be 50 resolved in order to accelerate progress towards the goal of ending the TB epidemic endorsed 51 by WHO [1]. 52 M. tuberculosis (MTB), has evolved successful mechanisms to circumvent the hostile 53 environment of the macrophage, such as inhibiting the phagosome-lysosome fusion and to 54 escape the acidic environment inside the phagolysosome [2]. MTB may be unique in its ability 55 to exploit adaptive immune responses, through inflammatory lung tissue damage, to promote 56 its transmission [3]. It has been proposed that this microorganism was pressed by an 57 evolutionary selection that resulted in an infection that induces partial immunity, where the 58 host survives a long period after being infected with the pathogen, aiding in microorganism 59 persistence and transmission [3]. MTB mechanisms of evasion of host immune system were 60 proposed to have c...

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Influenza virus N-linked glycosylation and innate immunity

Cited by 54 publications

References 177 publications

Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate

Integrative proteomic and glycoproteomic profiling of Mycobacterium tuberculosis culture filtrate

Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition

Proteomic profiling ofMycobacterium tuberculosisculture filtrate identifies novel O-glycosylated proteins

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