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

Yusang Xie, Hong Mei, Wei Wang, Xiao Li, Pengfei Hu, Xingui Tian, Rong Zhou, Jia Liu () and Jieming Qu ()
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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
Jia Liu: ShanghaiTech University
Jieming Qu: Diagnosis and Treatment of Respiratory Infectious Diseases

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-55261-3

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