Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.

Nuclear export and translation of intron-containing viral mRNAs are required for HIV-1 gene expression and replication. In this report, we provide evidence to show that DDX3 regulates the translation of HIV-1 mRNAs. We found that knockdown of DDX3 expression effectively inhibited HIV-1 production. T...

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Autores principales:	Ming-Chih Lai, Shainn-Wei Wang, Lie Cheng, Woan-Yuh Tarn, Shaw-Jenq Tsai, H Sunny Sun
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f49822152846479abedb09718b4b767b
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spelling	oai:doaj.org-article:f49822152846479abedb09718b4b767b2021-11-18T07:39:13ZHuman DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.1932-620310.1371/journal.pone.0068665https://doaj.org/article/f49822152846479abedb09718b4b767b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23840900/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Nuclear export and translation of intron-containing viral mRNAs are required for HIV-1 gene expression and replication. In this report, we provide evidence to show that DDX3 regulates the translation of HIV-1 mRNAs. We found that knockdown of DDX3 expression effectively inhibited HIV-1 production. Translation of HIV-1 early regulatory proteins, Tat and rev, was impaired in DDX3-depleted cells. All HIV-1 transcripts share a highly structured 5' untranslated region (UTR) with inhibitory elements on translation of viral mRNAs, yet DDX3 promoted translation of reporter mRNAs containing the HIV-1 5' UTR, especially with the transactivation response (TAR) hairpin. Interestingly, DDX3 directly interacts with HIV-1 Tat, a well-characterized transcriptional activator bound to the TAR hairpin. HIV-1 Tat is partially targeted to cytoplasmic stress granules upon DDX3 overexpression or cell stress conditions, suggesting a potential role of Tat/DDX3 complex in translation. We further demonstrated that HIV-1 Tat remains associated with translating mRNAs and facilitates translation of mRNAs containing the HIV-1 5' UTR. Taken together, these findings indicate that DDX3 is recruited to the TAR hairpin by interaction with viral Tat to facilitate HIV-1 mRNA translation.Ming-Chih LaiShainn-Wei WangLie ChengWoan-Yuh TarnShaw-Jenq TsaiH Sunny SunPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e68665 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ming-Chih Lai Shainn-Wei Wang Lie Cheng Woan-Yuh Tarn Shaw-Jenq Tsai H Sunny Sun Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.
description	Nuclear export and translation of intron-containing viral mRNAs are required for HIV-1 gene expression and replication. In this report, we provide evidence to show that DDX3 regulates the translation of HIV-1 mRNAs. We found that knockdown of DDX3 expression effectively inhibited HIV-1 production. Translation of HIV-1 early regulatory proteins, Tat and rev, was impaired in DDX3-depleted cells. All HIV-1 transcripts share a highly structured 5' untranslated region (UTR) with inhibitory elements on translation of viral mRNAs, yet DDX3 promoted translation of reporter mRNAs containing the HIV-1 5' UTR, especially with the transactivation response (TAR) hairpin. Interestingly, DDX3 directly interacts with HIV-1 Tat, a well-characterized transcriptional activator bound to the TAR hairpin. HIV-1 Tat is partially targeted to cytoplasmic stress granules upon DDX3 overexpression or cell stress conditions, suggesting a potential role of Tat/DDX3 complex in translation. We further demonstrated that HIV-1 Tat remains associated with translating mRNAs and facilitates translation of mRNAs containing the HIV-1 5' UTR. Taken together, these findings indicate that DDX3 is recruited to the TAR hairpin by interaction with viral Tat to facilitate HIV-1 mRNA translation.
format	article
author	Ming-Chih Lai Shainn-Wei Wang Lie Cheng Woan-Yuh Tarn Shaw-Jenq Tsai H Sunny Sun
author_facet	Ming-Chih Lai Shainn-Wei Wang Lie Cheng Woan-Yuh Tarn Shaw-Jenq Tsai H Sunny Sun
author_sort	Ming-Chih Lai
title	Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.
title_short	Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.
title_full	Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.
title_fullStr	Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.
title_full_unstemmed	Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.
title_sort	human ddx3 interacts with the hiv-1 tat protein to facilitate viral mrna translation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/f49822152846479abedb09718b4b767b
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Human DDX3 interacts with the HIV-1 Tat protein to facilitate viral mRNA translation.

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