Journal article
Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery
PloS one, v 7(7), 40662
10 Jul 2012
PMID: 22808228
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in some cases to produce novel viral miRNAs that can either assist in active viral infection or promote a latent state. Here, we show that HTLV-1 Tax contributes to the dysregulation of the RNAi pathway by altering the expression of key components of this pathway. A survey of uninfected and HTLV-1 infected cells revealed that Drosha protein is present at lower levels in all HTLV-1 infected cell lines and in infected primary cells, while other components such as DGCR8 were not dramatically altered. We show colocalization of Tax and Drosha in the nucleus in vitro as well as coimmunoprecipitation in the presence of proteasome inhibitors, indicating that Tax interacts with Drosha and may target it to specific areas of the cell, namely, the proteasome. In the presence of Tax we observed a prevention of primary miRNA cleavage by Drosha. Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus.
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Details
- Title
- Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery
- Creators
- Rachel Van Duyne - George Mason UniversityIrene Guendel - George Mason UniversityZachary Klase - National Institute of Allergy and Infectious DiseasesAarthi Narayanan - George Mason UniversityWilliam Coley - Washington University Medical CenterElizabeth Jaworski - George Mason UniversityJessica Roman - George Mason UniversityAnastas Popratiloff - George Washington UniversityRenaud Mahieux - Virologie et Pathologies HumainesKylene Kehn-Hall - George Mason UniversityFatah Kashanchi - George Mason University
- Publication Details
- PloS one, v 7(7), 40662
- Publisher
- Public Library Science
- Number of pages
- 14
- Grant note
- R21AI074410 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) George Mason university funds S10RR025565 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) AI078859; AI074410-01 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA 1S10RR025565 / National Center for Research Resources; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000306355500069
- Scopus ID
- 2-s2.0-84863661535
- Other Identifier
- 991021902505204721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology