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Structural insights...
Structural insights into the interaction between adenovirus C5 hexon and human lactoferrin
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- Dhillon, Arun (author)
- Institute of Organic Chemistry and Biochemistry, the Czech Academy of Sciences, Prague, Czech Republic
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- Persson, B. David (author)
- Swedish Veterinary Agency, Uppsala, Sweden
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- Volkov, Alexander N. (author)
- VIB-VUB Center for Structural Biology, Flemish Institute of Biotechnology (VIB), Brussels, Belgium; Jean Jeener NMR Centre, Vrije Universiteit Brussel (VUB), Brussels, Belgium
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- Sülzen, Hagen (author)
- Institute of Organic Chemistry and Biochemistry, the Czech Academy of Sciences, Prague, Czech Republic; Faculty of Science, Charles University, Prague, Czech Republic
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- Kádek, Alan (author)
- Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic; Leibniz Institute of Virology (LIV), Hamburg, Germany
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- Pompach, Petr (author)
- Biotechnology and Biomedical Center, the Academy of Sciences, Charles University in Vestec, Vestec, Czech Republic
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- Kereïche, Sami (author)
- Institute of Organic Chemistry and Biochemistry, the Czech Academy of Sciences, Prague, Czech Republic; First Faculty of Medicine, Charles University, Prague, Czech Republic
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- Lepšík, Martin (author)
- Institute of Organic Chemistry and Biochemistry, the Czech Academy of Sciences, Prague, Czech Republic
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- Danskog, Katarina (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Uetrecht, Charlotte (author)
- Department of Health Sciences and Biomedicine, Faculty V, School of Life Sciences, CSSB Centre for Structural Systems Biology, Deutsches Elektronen Synchrotron DESY, Leibniz Institute of Virology, Hamburg, University of Siegen, Siegen, Germany
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- Arnberg, Niklas, 1987- (author)
- Umeå universitet,Institutionen för klinisk mikrobiologi
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- Zoll, Sebastian (author)
- Institute of Organic Chemistry and Biochemistry, the Czech Academy of Sciences, Prague, Czech Republic
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(creator_code:org_t)
- 2024
- 2024
- English.
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In: Journal of Virology. - 0022-538X .- 1098-5514. ; 98:3
- Related links:
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https://doi.org/10.1...
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Abstract
Subject headings
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- Adenovirus (AdV) infection of the respiratory epithelium is common but poorly understood. Human AdV species C types, such as HAdV-C5, utilize the Coxsackieadenovirus receptor (CAR) for attachment and subsequently integrins for entry. CAR and integrins are however located deep within the tight junctions in the mucosa where they would not be easily accessible. Recently, a model for CAR-independent AdV entry was proposed. In this model, human lactoferrin (hLF), an innate immune protein, aids the viral uptake into epithelial cells by mediating interactions between the major capsid protein, hexon, and yet unknown host cellular receptor(s). However, a detailed understanding of the molecular interactions driving this mechanism is lacking. Here, we present a new cryo-EM structure of HAdV-5C hexon at high resolution alongside a hybrid structure of HAdV-5C hexon complexed with human lactoferrin (hLF). These structures reveal the molecular determinants of the interaction between hLF and HAdV-C5 hexon. hLF engages hexon primarily via its N-terminal lactoferricin (Lfcin) region, interacting with hexon’s hypervariable region 1 (HVR-1). Mutational analyses pinpoint critical Lfcin contacts and also identify additional regions within hLF that critically contribute to hexon binding. Our study sheds more light on the intricate mechanism by which HAdV-C5 utilizes soluble hLF/Lfcin for cellular entry. These findings hold promise for advancing gene therapy applications and inform vaccine development.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- adenovirus
- cryo-EM
- immune evasion
- lactoferrin
- viral entry
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Dhillon, Arun
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Persson, B. Davi ...
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Volkov, Alexande ...
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Sülzen, Hagen
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Kádek, Alan
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Pompach, Petr
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Kereïche, Sami
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Lepšík, Martin
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Danskog, Katarin ...
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Uetrecht, Charlo ...
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Arnberg, Niklas, ...
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Zoll, Sebastian
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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Journal of Virol ...
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Umeå University