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

Xie, Yusang; Mei, Hong; Wang, Wei; Li, Xiao; Hu, Pengfei; Tian, Xingui; Zhou, Rong; Liu, Jia; Qu, Jieming

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. Following a previous multicenter clinical study on severe community acquired pneumonia (SCAP), Profs. Qu and Liu groups here perform surface protein-focused CRISPR screens with SCAP-associated human adenovirus species B and identify ALCAM as an entry factor.

CELL adhesion molecules; MEDICAL sciences; COMMUNITY-acquired pneumonia; MEDICAL microbiology; GENETIC testing

Nature Communications, 2024, Vol 15, Issue 1, p1

2041-1723

Academic Journal

10.1038/s41467-024-55261-3