Identification of direct transcriptional targets of the Kaposi's sarcoma-associated herpesvirus Rta lytic switch protein by conditional nuclear localization.

Journal of Virology
Wei BuDavid M Lukac

Abstract

Lytic reactivation from latency is critical for the pathogenesis of Kaposi's sarcoma-associated herpesvirus (KSHV). We previously demonstrated that the 691-amino-acid (aa) KSHV Rta transcriptional transactivator is necessary and sufficient to reactivate the virus from latency. Viral lytic cycle genes, including those expressing additional transactivators and putative oncogenes, are induced in a cascade fashion following Rta expression. In this study, we sought to define Rta's direct targets during reactivation by generating a conditionally nuclear variant of Rta. Wild-type Rta protein is constitutively localized to cell nuclei and contains two putative nuclear localization signals (NLSs). Only one NLS (NLS2; aa 516 to 530) was required for the nuclear localization of Rta, and it relocalized enhanced green fluorescent protein exclusively to cell nuclei. The results of analyses of Rta NLS mutants demonstrated that proper nuclear localization of Rta was required for transactivation and the stimulation of viral reactivation. RTA with NLS1 and NLS2 deleted was fused to the hormone-binding domain of the murine estrogen receptor to generate an Rta variant whose nuclear localization and ability to transactivate and induce reactivation ...Continue Reading

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Citations

Jun 1, 2011·Advances in Virology·Fengchun YeShou-Jiang Gao
Jan 17, 2015·Viruses·Pravinkumar PurushothamanSubhash C Verma
Dec 17, 2014·Viruses·Timsy UppalErle S Robertson
May 21, 2016·Frontiers in Microbiology·Shuvomoy BanerjeeSubhash C Verma
Aug 5, 2017·Pathogens·Jennifer L DeCotiis, David M Lukac
Jun 9, 2020·Frontiers in Microbiology·Mel CampbellPei-Ching Chang
May 6, 2017·Frontiers in Microbiology·Kawalpreet K Aneja, Yan Yuan
Mar 8, 2020·Journal of Biomedical Science·Mel Campbell, Yoshihiro Izumiya
Aug 10, 2017·Pathogens·Jennifer L DeCotiis, David M Lukac

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