Atlastin Endoplasmic Reticulum-Shaping Proteins Facilitate Zika Virus Replication
| Autor: | Craig Blackstone, Samy Sid Ahmed, Philippe Roingeard, Françoise Porrot, Julien Burlaud-Gaillard, Sonia Amraoui, Ali Amara, Maaran Michael Rajah, Blandine Monel, Julian Buchrieser, Cécile Meunier, Maxime Chazal, Olivier Schwartz, Mohamed Lamine Hafirassou, Quentin Nevers, Peng-Peng Zhu, Nolwenn Jouvenet, Audrey Salles |
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| Rok vydání: | 2019 |
| Předmět: |
Atlastin
viruses Immunology Vacuole Biology Viral Nonstructural Proteins Endoplasmic Reticulum Virus Replication Microbiology Antiviral Agents Virus Zika virus GTP Phosphohydrolases 03 medical and health sciences Gene Knockout Techniques 0302 clinical medicine Cytopathogenic Effect Viral GTP-Binding Proteins Virology Humans Virus Release 030304 developmental biology 0303 health sciences Zika Virus Infection Endoplasmic reticulum Membrane Proteins Zika Virus biology.organism_classification 3. Good health Virus-Cell Interactions Flavivirus Viral replication Cytoplasm Insect Science 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | J Virol |
| ISSN: | 1098-5514 |
| Popis: | The endoplasmic reticulum (ER) is the site for Zika virus (ZIKV) replication and is central to the cytopathic effects observed in infected cells. ZIKV induces the formation of ER-derived large cytoplasmic vacuoles followed by “implosive” cell death. Little is known about the nature of the ER factors that regulate flavivirus replication. Atlastins (ATL1, -2, and -3) are dynamin-related GTPases that control the structure and the dynamics of the ER membrane. We show here that ZIKV replication is significantly decreased in the absence of ATL proteins. The appearance of infected cells is delayed, the levels of intracellular viral proteins and released virus are reduced, and the cytopathic effects are strongly impaired. We further show that ATL3 is recruited to viral replication sites and interacts with the nonstructural viral proteins NS2A and NS2B3. Thus, proteins that shape and maintain the ER tubular network ensure efficient ZIKV replication. IMPORTANCE Zika virus (ZIKV) is an emerging virus associated with Guillain-Barré syndrome, and fetal microcephaly as well as other neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We found that endoplasmic reticulum (ER)-shaping atlastin proteins (ATL1, -2, and -3), which induce ER membrane fusion, facilitate ZIKV replication. We show that ATL3 is recruited to the viral replication site and colocalize with the viral proteins NS2A and NS2B3. The results provide insights into host factors used by ZIKV to enhance its replication. |
| Databáze: | OpenAIRE |
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