Journal
SCIENCE ADVANCES
Volume 7, Issue 2, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abe0974
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Funding
- Human Frontier Science Program (Career Development Award) [CDA00047/2017-C]
- Stiftelsen Olle Engkvist Byggmastare
- Knut and Alice Wallenberg Foundation (Wallenberg Centre for Molecular Medicine Umea)
- Swedish Research Council [2019-01472, 2017-00859]
- Knut and Alice Wallenberg Foundation
- Kempe Foundations
- SNIC [2018/5-158, 2019/3-668, 2019/5-76]
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HAdV-F40 and F41 are major causes of diarrhea and diarrhea-related mortality in young children worldwide, with a structure that differs significantly from non-enteric HAdVs, providing new insights into HAdV architecture.
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 angstrom. 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.
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