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Efficient clathrin-mediated entry of enteric adenoviruses in human duodenal cells
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Department of Biochemistry, Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.ORCID iD: 0000-0002-3634-066x
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
Umeå University, Faculty of Medicine, Department of Clinical Microbiology. Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
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2023 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 97, no 10Article in journal (Refereed) Published
Abstract [en]

Enteric adenovirus types F40 and 41 (EAdVs) are a leading cause of diarrhea and diarrhea-associated death in young children and have recently been proposed to cause acute hepatitis in children. EAdVs have a unique capsid architecture and exhibit — unlike other human adenoviruses — a relatively strict tropism for gastrointestinal tissues with, to date, understudied infection mechanism and unknown target cells. In this study, we turn to potentially limiting host factors by comparing EAdV entry in cell lines with respiratory and intestinal origin by cellular perturbation, virus particle tracking, and transmission electron microscopy. Our analyses highlight kinetic advantages for EAdVs in duodenal HuTu80 cell infection and reveal a larger fraction of mobile particles, faster virus uptake, and infectious particle entry in intestinal cells. Moreover, EAdVs display a dependence on clathrin- and dynamin-dependent pathways in intestinal cells. Detailed knowledge of virus entry routes and host factor requirements is essential to understanding pathogenesis and developing new countermeasures. Hence, this study provides novel insights into the entry mechanisms of a medically important virus with emerging tropism in a cell line originating from a relevant tissue. IMPORTANCE Enteric adenoviruses have historically been difficult to grow in cell culture, which has resulted in lack of knowledge of host factors and pathways required for infection of these medically relevant viruses. Previous studies in non-intestinal cell lines showed slow infection kinetics and generated comparatively low virus yields compared to other adenovirus types. We suggest duodenum-derived HuTu80 cells as a superior cell line for studies to complement efforts using complex intestinal tissue models. We show that viral host cell factors required for virus entry differ between cell lines from distinct origins and demonstrate the importance of clathrin-mediated endocytosis.

Place, publisher, year, edition, pages
2023. Vol. 97, no 10
Keywords [en]
clathrin-mediated endocytosis, electron microscopy, enteric adenovirus, single particle tracking, virus entry
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-216662DOI: 10.1128/jvi.00770-23PubMedID: 37823645Scopus ID: 2-s2.0-85175844402OAI: oai:DiVA.org:umu-216662DiVA, id: diva2:1815024
Funder
Swedish Research Council, 2020-06242Swedish Research Council, 2019-01472Knut and Alice Wallenberg FoundationKnut and Alice Wallenberg FoundationAvailable from: 2023-11-27 Created: 2023-11-27 Last updated: 2023-11-28Bibliographically approved

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Becker, MiriamConca, Dario ValterDorma, NoemiMistry, NiteshHahlin, ElinFrängsmyr, LarsBally, MartaArnberg, NiklasGerold, Gisa

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Becker, MiriamConca, Dario ValterDorma, NoemiMistry, NiteshHahlin, ElinFrängsmyr, LarsBally, MartaArnberg, NiklasGerold, Gisa
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Department of Clinical MicrobiologyWallenberg Centre for Molecular Medicine at Umeå University (WCMM)Molecular Infection Medicine Sweden (MIMS)
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