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An Integrated Systems Biology Approach Identifies ZIKV and DENV Replication

Genomics, Proteomics & Bioinformatics 2021年第1期19卷 108-122页

作者： Guang Song Emily M.Lee Jianbo Pan Miao Xu Hee-Sool Rho Yichen Cheng Nadia Whitt Shu Yang Jennifer Kouznetsova carleen klumpp-thomas Samuel G.Michael Cedric Moore Ki-Jun Yoon Kimberly M.Christian Anton Simeonov Wenwei Huang Menghang Xia Ruili Huang Madhu Lal-Nag Hengli Tang Wei Zheng Jiang Qian Hongjun Song Guo-li Ming Heng Zhu Department of Pharmacology&Molecular Sciences Johns Hopkins School of MedicineBaltimoreMD 21205USA Department of Biological Science Florida State UniversityTallahasseeFL 32306USA Department of Ophthalmology Johns Hopkins School of MedicineBaltimoreMD 21205USA National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310016China Institute for Cell Engineering Johns Hopkins University School of MedicineBaltimoreMD 21205USA Department of Neuroscience and Mahoney Institute for Neurosciences Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Department of Cell and Developmental Biology Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA Institute for Regenerative Medicine Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA The Epigenetics Institute Perelman School for MedicineUniversity of PennsylvaniaPhiladelphiaPA 19104USA

The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease *** we employed three independent systems biology approaches toward this ***,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome ***,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this ***,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV *** analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV *** study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets.

关键词： Protein–protein interaction RNAi screening Chemical genetics screening Multi-omics

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Corrigendum to“An Integrated Systems Biology Approach Identifies the Proteasome as A Critical Host Machinery for ZIKV and DENV Replication"[Genomics Proteomics Bioinformatics 19(1)(2021)108-122]

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Genomics, Proteomics & Bioinformatics 2022年第4期20卷 808-809页

作者： Song, Guang Lee, Emily M. Pan, Jianbo Xu, Miao Rho, Hee-Sool Cheng, Yichen Whitt, Nadia Yang, Shu Kouznetsova, Jennifer klumpp-thomas, carleen Michael, Samuel G. Moore, Cedric Yoon, Ki-Jun Christian, Kimberly M. Simeonov, Anton Huang, Wenwei Xia, Menghang Huang, Ruili Lal-Nag, Madhu Tang, Hengli Zheng, Wei Qian, Jiang Song, Hongjun Ming, Guo-li Zhu, Heng Department of Pharmacology & Molecular Sciences Johns Hopkins School of Medicine Baltimore MD 21205 USA Department of Biological Science Florida State University Tallahassee FL 32306 USA Department of Ophthalmology Johns Hopkins School of Medicine Baltimore MD 21205 USA National Center for Advancing Translational Sciences National Institutes of Health Bethesda MD 20892 USA Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310016 China Institute for Cell Engineering Johns Hopkins University School of Medicine Baltimore MD 21205 USA Department of Neuroscience and Mahoney Institute for Neurosciences Perelman School for Medicine University of Pennsylvania Philadelphia PA 19104 USA Department of Cell and Developmental Biology Perelman School for Medicine University of Pennsylvania Philadelphia PA 19104 USA Institute for Regenerative Medicine Perelman School for Medicine University of Pennsylvania Philadelphia PA 19104 USA The Epigenetics Institute Perelman School for Medicine University of Pennsylvania Philadelphia PA 19104 USA

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