Alix Serves as an Adaptor That Allows Human Parainfluenza Virus Type 1 to Interact with the Host Cell ESCRT System
| العنوان: | Alix Serves as an Adaptor That Allows Human Parainfluenza Virus Type 1 to Interact with the Host Cell ESCRT System |
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| المؤلفون: | Alexander C. Schmidt, Henrick Schomacker, Jim Boonyaratanakornkit, Peter L. Collins |
| المصدر: | PLoS ONE PLoS ONE, Vol 8, Iss 3, p e59462 (2013) |
| بيانات النشر: | Public Library of Science, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Proteomics, Viral Diseases, lcsh:Medicine, Fluorescent Antibody Technique, Cell Cycle Proteins, Pathogenesis, Biochemistry, Mass Spectrometry, Calcium-binding protein, RNA, Small Interfering, lcsh:Science, Vacuolar protein sorting, Multidisciplinary, Reverse Transcriptase Polymerase Chain Reaction, Cell biology, ESCRT complex, Host-Pathogen Interaction, Infectious Diseases, Medicine, Research Article, Plasmids, Protein domain, Blotting, Western, Biology, Transfection, Microbiology, Binding, Competitive, ESCRT, Viral Proteins, Virology, Humans, Immunoprecipitation, Cell Cycle Protein, Protein Interactions, DNA Primers, Endosomal Sorting Complexes Required for Transport, lcsh:R, Calcium-Binding Proteins, Proteins, Viral Vaccines, Molecular biology, Viral Replication, Parainfluenza Virus 1, Human, Membrane protein, Viral replication, Virulence Factors and Mechanisms, lcsh:Q, Human Parainfluenza Virus Infection, Viral Transmission and Infection |
| الوصف: | The cellular ESCRT (endosomal sorting complex required for transport) system functions in cargo-sorting, in the formation of intraluminal vesicles that comprise multivesicular bodies (MVB), and in cytokinesis, and this system can be hijacked by a number of enveloped viruses to promote budding. The respiratory pathogen human parainfluenza virus type I (HPIV1) encodes a nested set of accessory C proteins that play important roles in down-regulating viral transcription and replication, in suppressing the type I interferon (IFN) response, and in suppressing apoptosis. Deletion or mutation of the C proteins attenuates HPIV1 in vivo, and such mutants are being evaluated preclinically and clinically as vaccines. We show here that the C proteins interact and co-localize with the cellular protein Alix, which is a member of the class E vacuolar protein sorting (Vps) proteins that assemble at endosomal membranes into ESCRT complexes. The HPIV1 C proteins interact with the Bro1 domain of Alix at a site that is also required for the interaction between Alix and Chmp4b, a subunit of ESCRT-III. The C proteins are ubiquitinated and subjected to proteasome-mediated degradation, but the interaction with AlixBro1 protects the C proteins from degradation. Neither over-expression nor knock-down of Alix expression had an effect on HPIV1 replication, although this might be due to the large redundancy of Alix-like proteins. In contrast, knocking down the expression of Chmp4 led to an approximately 100-fold reduction in viral titer during infection with wild-type (WT) HPIV1. This level of reduction was similar to that observed for the viral mutant, P(C-) HPIV1, in which expression of the C proteins were knocked out. Chmp4 is capable of out-competing the HPIV1 C proteins for binding Alix. Together, this suggests a possible model in which Chmp4, through Alix, recruits the C proteins to a common site on intracellular membranes and facilitates budding. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::63e6e6106ef206cf1924f017ad0ffed3Test http://europepmc.org/articles/PMC3602193Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....63e6e6106ef206cf1924f017ad0ffed3 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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