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ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B

Author

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  • Yusang Xie

    (Diagnosis and Treatment of Respiratory Infectious Diseases)

  • Hong Mei

    (ShanghaiTech University)

  • Wei Wang

    (ShanghaiTech University)

  • Xiao Li

    (Guangzhou Medical University)

  • Pengfei Hu

    (ShanghaiTech University)

  • Xingui Tian

    (Guangzhou Medical University)

  • Rong Zhou

    (Guangzhou Medical University
    Guangzhou)

  • Jia Liu

    (ShanghaiTech University
    Guangzhou
    Shanghai Clinical Research and Trial Center)

  • Jieming Qu

    (Diagnosis and Treatment of Respiratory Infectious Diseases)

Abstract

Human adenovirus (HAdV) is a widely spread respiratory pathogen that can cause infections in multiple tissues and organs. Previous studies have established an association between HAdV species B (HAdV-B) infection and severe community-acquired pneumonia (SCAP). However, the connection between SCAP-associated HAdV-B infection and host factor expression profile in patients has not been systematically investigated. Here, we perform a CRISPR genetic screen on HAdV-B using two generations of cell surface protein-focused CRISPR libraries and identify a series of host factors including the known receptor DSG-2 and an unknown factor, activated leukocyte cell adhesion molecule (ALCAM). Further investigation shows that ALCAM affects HAdV-B infection by participating in viral internalization. Transcriptomics data from human blood samples suggests that ALCAM expression is higher in SCAP patients with HAdV-B infection than in those with other infections. Chimeric and authentic virus experiments show that ALCAM is a widely used host factor across B1 and B2 genetic clusters of HAdV-B. The dissociation constant between the knob domain of HAdV-B fiber and ALCAM is 837 nM in average. In summary, our results suggest that ALCAM is an entry factor for SCAP-associated HAdV-B.

Suggested Citation

  • Yusang Xie & Hong Mei & Wei Wang & Xiao Li & Pengfei Hu & Xingui Tian & Rong Zhou & Jia Liu & Jieming Qu, 2024. "ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-55261-3
    DOI: 10.1038/s41467-024-55261-3
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