Your browser doesn't support javascript.
Human species D adenovirus hexon capsid protein mediates cell entry through a direct interaction with CD46.
Persson, B David; John, Lijo; Rafie, Karim; Strebl, Michael; Frängsmyr, Lars; Ballmann, Monika Z; Mindler, Katja; Havenga, Menzo; Lemckert, Angelique; Stehle, Thilo; Carlson, Lars-Anders; Arnberg, Niklas.
  • Persson BD; Department of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden.
  • John L; Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.
  • Rafie K; Department of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden.
  • Strebl M; Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.
  • Frängsmyr L; Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.
  • Ballmann MZ; Wallenberg Centre for Molecular Medicine, Umeå University, SE-90187 Umeå, Sweden.
  • Mindler K; Department of Medical Biochemistry, Umeå University, SE-90187 Umeå, Sweden.
  • Havenga M; Interfaculty Institute of Biochemistry, The University of Tübingen, D-72076 Tübingen, Germany.
  • Lemckert A; Department of Clinical Microbiology, Division of Virology, Umeå University, SE-90185 Umeå, Sweden.
  • Stehle T; Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.
  • Carlson LA; Batavia Biosciences, 2333 CL Leiden, The Netherlands.
  • Arnberg N; Interfaculty Institute of Biochemistry, The University of Tübingen, D-72076 Tübingen, Germany.
Proc Natl Acad Sci U S A ; 118(3)2021 01 19.
Article in English | MEDLINE | ID: covidwho-1003394
Semantic information from SemMedBD (by NLM)
1. Host Cell LOCATION_OF receptor
Subject
Host Cell
Predicate
LOCATION_OF
Object
receptor
2. CD46 PART_OF soluble
Subject
CD46
Predicate
PART_OF
Object
soluble
3. Protein Overexpression PROCESS_OF CD46
Subject
Protein Overexpression
Predicate
PROCESS_OF
Object
CD46
4. Cell Count USES CD46
Subject
Cell Count
Predicate
USES
Object
CD46
5. CD46 INTERACTS_WITH Scleroproteins
Subject
CD46
Predicate
INTERACTS_WITH
Object
Scleroproteins
6. Hexamethonium INTERACTS_WITH CD46
Subject
Hexamethonium
Predicate
INTERACTS_WITH
Object
CD46
7. soluble LOCATION_OF Hexamethonium
Subject
soluble
Predicate
LOCATION_OF
Object
Hexamethonium
8. CD46 INTERACTS_WITH Hexamethonium
Subject
CD46
Predicate
INTERACTS_WITH
Object
Hexamethonium
9. Host Cell LOCATION_OF receptor
Subject
Host Cell
Predicate
LOCATION_OF
Object
receptor
10. CD46 PART_OF soluble
Subject
CD46
Predicate
PART_OF
Object
soluble
11. Protein Overexpression PROCESS_OF CD46
Subject
Protein Overexpression
Predicate
PROCESS_OF
Object
CD46
12. Cell Count USES CD46
Subject
Cell Count
Predicate
USES
Object
CD46
13. CD46 INTERACTS_WITH Scleroproteins
Subject
CD46
Predicate
INTERACTS_WITH
Object
Scleroproteins
14. Hexamethonium INTERACTS_WITH CD46
Subject
Hexamethonium
Predicate
INTERACTS_WITH
Object
CD46
15. soluble LOCATION_OF Hexamethonium
Subject
soluble
Predicate
LOCATION_OF
Object
Hexamethonium
16. CD46 INTERACTS_WITH Hexamethonium
Subject
CD46
Predicate
INTERACTS_WITH
Object
Hexamethonium
ABSTRACT
Human adenovirus species D (HAdV-D) types are currently being explored as vaccine vectors for coronavirus disease 2019 (COVID-19) and other severe infectious diseases. The efficacy of such vector-based vaccines depends on functional interactions with receptors on host cells. Adenoviruses of different species are assumed to enter host cells mainly by interactions between the knob domain of the protruding fiber capsid protein and cellular receptors. Using a cell-based receptor-screening assay, we identified CD46 as a receptor for HAdV-D56. The function of CD46 was validated in infection experiments using cells lacking and overexpressing CD46, and by competition infection experiments using soluble CD46. Remarkably, unlike HAdV-B types that engage CD46 through interactions with the knob domain of the fiber protein, HAdV-D types infect host cells through a direct interaction between CD46 and the hexon protein. Soluble hexon proteins (but not fiber knob) inhibited HAdV-D56 infection, and surface plasmon analyses demonstrated that CD46 binds to HAdV-D hexon (but not fiber knob) proteins. Cryoelectron microscopy analysis of the HAdV-D56 virion-CD46 complex confirmed the interaction and showed that CD46 binds to the central cavity of hexon trimers. Finally, soluble CD46 inhibited infection by 16 out of 17 investigated HAdV-D types, suggesting that CD46 is an important receptor for a large group of adenoviruses. In conclusion, this study identifies a noncanonical entry mechanism used by human adenoviruses, which adds to the knowledge of adenovirus biology and can also be useful for development of adenovirus-based vaccine vectors.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Gene Expression Regulation, Viral / Adenoviruses, Human / Capsid Proteins / Virus Internalization / COVID-19 Vaccines / SARS-CoV-2 Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2020732118

Full text: Available Collection: International databases Database: MEDLINE Main subject: Gene Expression Regulation, Viral / Adenoviruses, Human / Capsid Proteins / Virus Internalization / COVID-19 Vaccines / SARS-CoV-2 Limits: Humans Language: English Year: 2021 Document Type: Article Affiliation country: Pnas.2020732118