Differential and convergent utilization of autophagy components by positive-strand RNA viruses
| Autor: | Nicholas van Buuren, Sara W. Bird, Roberto Mateo, Karim Majzoub, Emma Abernathy, Karla Kirkegaard, Jan E. Carette |
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| Přispěvatelé: | Bodescot, Myriam, Department of Genetics [Stanford], Stanford Medicine, Stanford University-Stanford University, Department of Microbiology and Immunology [Stanford], Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Jane Coffin Childs Postdoctoral Fellowship JCCfund.org (to EA). National Institutes of Allergy and Infectious Disease (grant number U19-A109662). National Institutes of Health (grant number R56-AI103500). National Institutes of Health (grant number DP2 AI104557). (to JEC). Stanford Child Health Research Institute (to KM). Stanford University School of Medicine. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
RNA viruses viruses Cultured tumor cells Autophagy-Related Proteins Dengue virus medicine.disease_cause Virus Replication Pathology and Laboratory Medicine Biochemistry Zika virus Enteroviruses Dengue 0302 clinical medicine Medicine and Health Sciences Biology (General) biology Cell Death Zika Virus Infection General Neuroscience Poliovirus Lipids 3. Good health Cell biology Virus Diseases Cell Processes Medical Microbiology Viral Pathogens Viruses RNA Viral Cell lines Pathogens General Agricultural and Biological Sciences Biological cultures Research Article QH301-705.5 Autophagic Cell Death [SDV.BC]Life Sciences [q-bio]/Cellular Biology Sciences du Vivant [q-bio]/Médecine humaine et pathologie Microbiology General Biochemistry Genetics and Molecular Biology Virus Cell Line 03 medical and health sciences Virology medicine Autophagy Humans HeLa cells Gene Microbial Pathogens [SDV.BC] Life Sciences [q-bio]/Cellular Biology General Immunology and Microbiology Flaviviruses Organisms RNA Biology and Life Sciences Zika Virus Cell Biology Dengue Virus biology.organism_classification Cell cultures Viral Replication Research and analysis methods 030104 developmental biology Viral replication 030217 neurology & neurosurgery Poliomyelitis |
| Zdroj: | PLoS Biology PLoS Biology, 2019, 17 (1), pp.e2006926. ⟨10.1371/journal.pbio.2006926⟩ PLoS Biology, Vol 17, Iss 1, p e2006926 (2019) PLoS Biology, Public Library of Science, 2019, 17 (1), pp.e2006926. ⟨10.1371/journal.pbio.2006926⟩ |
| ISSN: | 1544-9173 1545-7885 |
| Popis: | Many viruses interface with the autophagy pathway, a highly conserved process for recycling cellular components. For three viral infections in which autophagy constituents are proviral (poliovirus, dengue, and Zika), we developed a panel of knockouts (KOs) of autophagy-related genes to test which components of the canonical pathway are utilized. We discovered that each virus uses a distinct set of initiation components; however, all three viruses utilize autophagy-related gene 9 (ATG9), a lipid scavenging protein, and LC3 (light-chain 3), which is involved in membrane curvature. These results show that viruses use noncanonical routes for membrane sculpting and LC3 recruitment. By measuring viral RNA abundance, we also found that poliovirus utilizes these autophagy components for intracellular growth, while dengue and Zika virus only use autophagy components for post-RNA replication processes. Comparing how RNA viruses manipulate the autophagy pathway reveals new noncanonical autophagy routes, explains the exacerbation of disease by starvation, and uncovers common targets for antiviral drugs. Author summary Viruses often co-opt host cellular processes to replicate their genomes and spread to other cells. Many of these cellular pathways provide good targets for antiviral drugs, as they are less likely to develop resistance since they are encoded in the host and not the fast-evolving viral genome. The autophagy pathway is an important stress response pathway that allows cells to recycle cellular components for energy conservation by sequestering cytoplasmic molecules and organelles in double-membraned vesicles (DMVs) and by degrading the contents into reusable elements. Many RNA viruses induce this pathway to provide membrane surfaces for replication and as a source of vesicles for maturation and exit from cells. We developed a panel of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) knockout (KO) human cells lacking individual components of the autophagy pathway to assess what aspects of the pathway diverse RNA viruses utilized. We discovered that poliovirus, dengue virus, and Zika virus all use different initiation components of the autophagy pathway but similar downstream components. Additionally, we found that poliovirus uses autophagy components for genome replication, while dengue and Zika viruses use autophagy components for postreplication processes. Ultimately, we uncovered potential drug targets for multiple RNA viruses. |
| Databáze: | OpenAIRE |
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