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Human adenovirus (HAdV)-F40 and -F41 are leading causes of diarrhea and diarrhea-associated mortality in children under the age of five, but the mechanisms by which they infect host cells are poorly understood. HAdVs initiate infection through interactions between the knob domain of the fiber capsid protein and host cell receptors. Unlike most other HAdVs, HAdV-F40 and -F41 possess two different fiber proteins—a long fiber and a short fiber. Whereas the long fiber binds to the Coxsackievirus and adenovirus receptor (CAR), no binding partners have been identified for the short fiber. In this study, we identified heparan sulfate (HS) as an interaction partner for the short fiber of enteric HAdVs. We demonstrate that exposure to acidic pH, which mimics the environment of the stomach, inactivates the interaction of enteric adenovirus with CAR. However, the short fiber:HS interaction is resistant to and even enhanced by acidic pH, which allows attachment to host cells. Our results suggest a switch in receptor usage of enteric HAdVs after exposure to acidic pH and add to the understanding of the function of the short fibers. These results may also be useful for antiviral drug development and the utilization of enteric HAdVs for clinical applications such as vaccine development.
Anandi Rajan; Elin Palm; Fredrik Trulsson; Sarah Mundigl; Miriam Becker; B. Persson; Lars Frängsmyr; AnnaSara Lenman. Heparan Sulfate Is a Cellular Receptor for Enteric Human Adenoviruses. Viruses 2021, 13, 298 .
AMA StyleAnandi Rajan, Elin Palm, Fredrik Trulsson, Sarah Mundigl, Miriam Becker, B. Persson, Lars Frängsmyr, AnnaSara Lenman. Heparan Sulfate Is a Cellular Receptor for Enteric Human Adenoviruses. Viruses. 2021; 13 (2):298.
Chicago/Turabian StyleAnandi Rajan; Elin Palm; Fredrik Trulsson; Sarah Mundigl; Miriam Becker; B. Persson; Lars Frängsmyr; AnnaSara Lenman. 2021. "Heparan Sulfate Is a Cellular Receptor for Enteric Human Adenoviruses." Viruses 13, no. 2: 298.
Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ notably in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here, we present the first structure of an enteric HAdV—HAdV-F41—determined by cryo–electron microscopy to a resolution of 3.8 Å. The structure reveals extensive alterations to the virion exterior as compared to nonenteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of core protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation of enteric HAdVs to a fundamentally different tissue tropism.
K. Rafie; A. Lenman; J. Fuchs; A. Rajan; N. Arnberg; L.-A. Carlson. The structure of enteric human adenovirus 41—A leading cause of diarrhea in children. Science Advances 2021, 7, eabe0974 .
AMA StyleK. Rafie, A. Lenman, J. Fuchs, A. Rajan, N. Arnberg, L.-A. Carlson. The structure of enteric human adenovirus 41—A leading cause of diarrhea in children. Science Advances. 2021; 7 (2):eabe0974.
Chicago/Turabian StyleK. Rafie; A. Lenman; J. Fuchs; A. Rajan; N. Arnberg; L.-A. Carlson. 2021. "The structure of enteric human adenovirus 41—A leading cause of diarrhea in children." Science Advances 7, no. 2: eabe0974.
Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ strikingly in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here we present the first structure of an enteric HAdV - HAdV-F41 - determined by cryo-EM to a resolution of 3.8Å. The structure reveals extensive alterations to the virion exterior as compared to non-enteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation to a fundamentally different tissue tropism of enteric HAdVs.
Karim Rafie; AnnaSara Lenman; Johannes Fuchs; Anandi Rajan; Niklas Arnberg; Lars-Anders Carlson. The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children. 2020, 1 .
AMA StyleKarim Rafie, AnnaSara Lenman, Johannes Fuchs, Anandi Rajan, Niklas Arnberg, Lars-Anders Carlson. The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children. . 2020; ():1.
Chicago/Turabian StyleKarim Rafie; AnnaSara Lenman; Johannes Fuchs; Anandi Rajan; Niklas Arnberg; Lars-Anders Carlson. 2020. "The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children." , no. : 1.