Key result
Enteric adenoviruses enter duodenal cells faster than respiratory cells via a clathrin- and dynamin-dependent pathway.
Why the study?
Enteric adenovirus types F40 and 41 have a relatively strict tropism for gastrointestinal tissues with understudied infection mechanisms, unknown target cells, and poorly understood host factor requirements.
Enteric adenoviruses utilize clathrin- and dynamin-dependent endocytosis for efficient entry into human duodenal cells, providing a superior in vitro model for studying their pathogenesis.
Establishes HuTu80 cells as a model for enteric adenovirus entry; leaves open in vivo validation and clinical relevance.
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.
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Becker et al. (2023) studied Enteric adenovirus infection. Enteric adenovirus (EAdV) infection vs. A549 respiratory cells was evaluated on Viral uptake kinetics and infectious internalization. Enteric adenoviruses exhibit faster uptake and infectious entry in duodenal HuTu80 cells compared to respiratory A549 cells, utilizing a clathrin- and dynamin-dependent pathway.
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