Localization and sub-cellular shuttling of HTLV-1 tax with the miRNA machinery

Authors

Rachel Van Duyne, George Washington University
Irene Guendel, George Mason University
Zachary Klase, National Institutes of Health, Bethesda, MD
Aarthi Narayanan, George Mason University
William Coley, George Washington University
Elizabeth Jaworski, George Mason University
Jessica Roman, George Mason UniversityFollow
Anastas Popratiloff, George Washington UniversityFollow
Renaud Mahieux, Retroviral Oncogenesis Team, INSERM-U758 Virologie Humaine, Lyon, France
Kylene Kehn-Hall, George Mason University
Fatah Kashanchi, George Washington UniversityFollow

Document Type

Journal Article

Publication Date

2012

Journal

PLoS ONE

Volume

Volume 7, Issue 7

Inclusive Pages

Article Number e40662

Keywords

Gene Products--metabolism; Human T-lymphotropic virus 1--metabolism; MicroRNAs--metabolism

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.

Comments

Reproduced with permission of PLoS ONE

APA Citation

Van Duyne, R., Guendel, I., Klase, Z., Narayanan, A., Coley, W., Jaworski, E., Roman, J., Popratiloff, A., Mahieux, R., Kehn-Hall, K., Kashanchi, F. (2012). Localization and sub-cellular shuttling of HTLV-1 tax with the miRNA machinery. PLoS ONE, 7(7), article number e40662.

Peer Reviewed

1

Open Access

1