ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B
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 betwee...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55261-3 |
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| author | Yusang Xie Hong Mei Wei Wang Xiao Li Pengfei Hu Xingui Tian Rong Zhou Jia Liu Jieming Qu |
| author_facet | Yusang Xie Hong Mei Wei Wang Xiao Li Pengfei Hu Xingui Tian Rong Zhou Jia Liu Jieming Qu |
| author_sort | Yusang Xie |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-34f9c4b108f045bf94f68e267a59f12d |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-34f9c4b108f045bf94f68e267a59f12d2025-01-05T12:36:02ZengNature PortfolioNature Communications2041-17232024-12-0115111310.1038/s41467-024-55261-3ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species BYusang Xie0Hong Mei1Wei Wang2Xiao Li3Pengfei Hu4Xingui Tian5Rong Zhou6Jia Liu7Jieming Qu8Department 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 DiseasesShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityState Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical UniversityShanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech UniversityDepartment 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 DiseasesAbstract 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.https://doi.org/10.1038/s41467-024-55261-3 |
| spellingShingle | Yusang Xie Hong Mei Wei Wang Xiao Li Pengfei Hu Xingui Tian Rong Zhou Jia Liu Jieming Qu ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B Nature Communications |
| title | ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B |
| title_full | ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B |
| title_fullStr | ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B |
| title_full_unstemmed | ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B |
| title_short | ALCAM is an entry factor for severe community acquired Pneumonia-associated Human adenovirus species B |
| title_sort | alcam is an entry factor for severe community acquired pneumonia associated human adenovirus species b |
| url | https://doi.org/10.1038/s41467-024-55261-3 |
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