RNA interference screen for human genes associated with West Nile virus infection
| Autor: | Hameeda Sultana, Pradeep D. Uchil, Aylwin Ng, Peter W. Mason, Stephen J. Elledge, Sima Lev, Ramnik J. Xavier, Abraham L. Brass, Melody Tsui, Hervé Agaisse, Erol Fikrig, Feng Qian, Rachel Adametz, Manoj N. Krishnan, Raymond A. Koski, Ruth R. Montgomery, Felicia D. Gilfoy, Bindu Sukumaran |
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| Rok vydání: | 2008 |
| Předmět: |
Monocarboxylic Acid Transporters
viruses Ubiquitin-Protein Ligases Muscle Proteins Dengue virus medicine.disease_cause Endoplasmic Reticulum Virus Replication Virus Article Dengue fever RNA interference medicine Humans Host factor Multidisciplinary biology Genome Human Gene Expression Profiling Immunity Ubiquitination virus diseases Computational Biology HIV RNA virus Vesiculovirus Dengue Virus biology.organism_classification medicine.disease Virology Flavivirus Viral replication RNA Interference West Nile virus West Nile Fever HeLa Cells Protein Binding |
| Zdroj: | Nature. 455(7210) |
| ISSN: | 1476-4687 |
| Popis: | West Nile virus (WNV), and related flaviviruses such as tick-borne encephalitis, Japanese encephalitis, yellow fever and dengue viruses, constitute a significant global human health problem1. However, our understanding of the molecular interaction of WNV (and related flaviviruses) with mammalian host cells is limited1. WNV encodes only 10 proteins, implying that the virus may use many cellular proteins for infection1. WNV enters the cytoplasm through pH-dependent endocytosis, undergoes cycles of translation and replication, assembles progeny virions in association with endoplasmic reticulum, and exits along the secretory pathway1–3. RNA-interference (RNAi) presents a powerful forward genetics approach to dissect virus-host cell interactions4–6. Here we report the identification of 305 host proteins impacting WNV infection, using a human genome-wide RNAi screen. Functional clustering of the genes revealed a complex dependence of this virus on host cell physiology, requiring a wide variety of molecules and cellular pathways for successful infection. We further demonstrate a requirement for the ubiquitin ligase CBLL1 in WNV internalization, a post-entry role for the endoplasmic reticulum-associated degradation (ERAD) pathway in viral infection, and the monocarboxylic acid transporter MCT4 as a viral replication resistance factor. By extending this study to dengue virus, we show that flaviviruses have both overlapping and unique interaction strategies with host cells. This study provides the first comprehensive molecular portrait of WNV-human cell interactions that forms a paradigm for understanding single plus-stranded RNA virus infection, and reveals potential antiviral targets. |
| Databáze: | OpenAIRE |
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