دورية أكاديمية

The Race against Protease Activation Defines the Role of ESCRTs in HIV Budding.

التفاصيل البيبلوغرافية
العنوان: The Race against Protease Activation Defines the Role of ESCRTs in HIV Budding.
المؤلفون: Mourad Bendjennat, Saveez Saffarian
المصدر: PLoS Pathogens, Vol 12, Iss 6, p e1005657 (2016)
بيانات النشر: Public Library of Science (PLoS), 2016.
سنة النشر: 2016
المجموعة: LCC:Immunologic diseases. Allergy
LCC:Biology (General)
مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
الوصف: HIV virions assemble on the plasma membrane and bud out of infected cells using interactions with endosomal sorting complexes required for transport (ESCRTs). HIV protease activation is essential for maturation and infectivity of progeny virions, however, the precise timing of protease activation and its relationship to budding has not been well defined. We show that compromised interactions with ESCRTs result in delayed budding of virions from host cells. Specifically, we show that Gag mutants with compromised interactions with ALIX and Tsg101, two early ESCRT factors, have an average budding delay of ~75 minutes and ~10 hours, respectively. Virions with inactive proteases incorporated the full Gag-Pol and had ~60 minutes delay in budding. We demonstrate that during budding delay, activated proteases release critical HIV enzymes back to host cytosol leading to production of non-infectious progeny virions. To explain the molecular mechanism of the observed budding delay, we modulated the Pol size artificially and show that virion release delays are size-dependent and also show size-dependency in requirements for Tsg101 and ALIX. We highlight the sensitivity of HIV to budding "on-time" and suggest that budding delay is a potent mechanism for inhibition of infectious retroviral release.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1553-7366
1553-7374
Relation: http://europepmc.org/articles/PMC4900648?pdf=render; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374
DOI: 10.1371/journal.ppat.1005657
URL الوصول: https://doaj.org/article/ced50353f2734aaf94ad74674f2bbd76
رقم الأكسشن: edsdoj.50353f2734aaf94ad74674f2bbd76
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:15537366
15537374
DOI:10.1371/journal.ppat.1005657