Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus
| العنوان: | Mutation of CD2AP and SH3KBP1 Binding Motif in Alphavirus nsP3 Hypervariable Domain Results in Attenuated Virus |
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| المؤلفون: | Andres Merits, Gerald M. McInerney, Aleksei Lulla, Sergo Kasvandik, Margit Mutso, Valeria Lulla, Mona Teppor, Margus Varjak, Liisi Tarve, Muriel Aquilimeba, Cecilia Smedberg, Bastian Thaa, Sirle Saul, Ainhoa Moliner Morro |
| المصدر: | Viruses Viruses, Vol 10, Iss 5, p 226 (2018) Viruses; Volume 10; Issue 5; Pages: 226 |
| بيانات النشر: | MDPI, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, viruses, Amino Acid Motifs, lcsh:QR1-502, RNA-dependent RNA polymerase, SH3 ligand, Alphavirus, CD2AP, SH3KBP1, Viral Nonstructural Proteins, Semliki Forest virus, medicine.disease_cause, Virus Replication, Virus, lcsh:Microbiology, Article, Cell Line, 03 medical and health sciences, proteomics, Virology, Cricetinae, medicine, Animals, Humans, Chikungunya, Binding site, Adaptor Proteins, Signal Transducing, CapZ Actin Capping Protein, NSP1, alphavirus, Chikungunya virus, Binding Sites, biology, virus diseases, biology.organism_classification, Semliki forest virus, Cytoskeletal Proteins, 030104 developmental biology, Infectious Diseases, Togaviridae, Host-Pathogen Interactions, Mutation, Protein Binding |
| الوصف: | Infection by Chikungunya virus (CHIKV) of the Old World alphaviruses (family Togaviridae) in humans can cause arthritis and arthralgia. The virus encodes four non-structural proteins (nsP) (nsP1, nsp2, nsP3 and nsP4) that act as subunits of the virus replicase. These proteins also interact with numerous host proteins and some crucial interactions are mediated by the unstructured C-terminal hypervariable domain (HVD) of nsP3. In this study, a human cell line expressing EGFP tagged with CHIKV nsP3 HVD was established. Using quantitative proteomics, it was found that CHIKV nsP3 HVD can bind cytoskeletal proteins, including CD2AP, SH3KBP1, CAPZA1, CAPZA2 and CAPZB. The interaction with CD2AP was found to be most evident; its binding site was mapped to the second SH3 ligand-like element in nsP3 HVD. Further assessment indicated that CD2AP can bind to nsP3 HVDs of many different New and Old World alphaviruses. Mutation of the short binding element hampered the ability of the virus to establish infection. The mutation also abolished ability of CD2AP to co-localise with nsP3 and replication complexes of CHIKV; the same was observed for Semliki Forest virus (SFV) harbouring a similar mutation. Similar to CD2AP, its homolog SH3KBP1 also bound the identified motif in CHIKV and SFV nsP3. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1999-4915 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bdd1ff2bbc27870ade9682b2c737bf87Test http://europepmc.org/articles/PMC5977219Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....bdd1ff2bbc27870ade9682b2c737bf87 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19994915 |
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