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Updated: Jun 4, 2025
Author Spotlight: Improved Method for Production and Purification of Adeno-Associated Viral Vectors
Published on: April 5, 2024
ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B
Yusang Xie1, Hong Mei2, Wei Wang2
1Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Institutes of Respiratory Diseases, School of Medicine, Shanghai Jiao Tong University and Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases, Shanghai, China.
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.
Insights
Activated leukocyte cell adhesion molecule (ALCAM) is identified as a novel entry factor for human adenovirus species B (HAdV-B) infections. This finding advances understanding of severe community-acquired pneumonia (SCAP) pathogenesis.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Human adenovirus (HAdV) causes widespread infections, with HAdV species B (HAdV-B) linked to severe community-acquired pneumonia (SCAP).
- The host factors influencing SCAP-associated HAdV-B infection require systematic investigation.
Purpose of the Study:
- To identify host factors involved in HAdV-B infection using CRISPR screening.
- To investigate the role of identified host factors in viral entry and their association with SCAP.
Main Methods:
- Conducted a CRISPR genetic screen using cell surface protein-focused libraries to identify HAdV-B host factors.
- Performed further investigations including viral internalization assays, transcriptomics analysis of patient blood samples, and chimeric/authentic virus experiments.
- Characterized the binding affinity between HAdV-B fiber knob and the identified host factor.
Main Results:
- Identified activated leukocyte cell adhesion molecule (ALCAM) as a novel host factor for HAdV-B infection, alongside the known receptor DSG-2.
- ALCAM facilitates HAdV-B entry by participating in viral internalization.
- ALCAM expression is elevated in SCAP patients with HAdV-B infection compared to other infections.
- ALCAM serves as a host factor across HAdV-B genetic clusters B1 and B2, with an average dissociation constant of 837 nM for HAdV-B fiber knob binding.
Conclusions:
- Activated leukocyte cell adhesion molecule (ALCAM) is a significant entry factor for severe community-acquired pneumonia-associated human adenovirus species B.
- This discovery provides new insights into HAdV-B pathogenesis and potential therapeutic targets.
