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.

人类腺病毒 (HAdV) F40 和 F41 型是全球幼儿腹泻和腹泻相关死亡率的主要原因。这些肠道 HAdV 在组织嗜性和致病性方面与呼吸道和眼部腺病毒显着不同，但这种差异的结构基础尚不清楚。在这里，我们展示了肠溶性 HAdV 的第一个结构——HAdV-F4​​1——通过低温电子显微镜测定，分辨率为 3.8 Å。与非肠道 HAdV 相比，该结构揭示了病毒粒子外部的广泛改变，包括衣壳蛋白 IX 的独特排列。该结构还为 HAdV 结构的保守方面提供了新的见解，例如核心蛋白 V 的拟议位置，它将病毒 DNA 与衣壳连接起来，以及组装诱导的五邻体碱基蛋白的构象变化。