ARID3B: A novel regulator of the Kaposi's sarcoma-associated herpesvirus lytic cycle

Jennifer J. Wood, James R. Boyne, Christina Paulus, Brian R. Jackson, Michael M. Nevels, Adrian Whitehouse, David J. Hughes

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of commonly fatal malignancies of immunocompromised individuals, including primary effusion lymphoma (PEL) and Kaposi's sarcoma (KS). A hallmark of all herpesviruses is their biphasic life cycle-viral latency and the productive lytic cycle-and it is well established that reactivation of the KSHV lytic cycle is associated with KS pathogenesis. Therefore, a thorough appreciation of the mechanisms that govern reactivation is required to better understand disease progression. The viral protein replication and transcription activator (RTA) is the KSHV lytic switch protein due to its ability to drive the expression of various lytic genes, leading to reactivation of the entire lytic cycle. While the mechanisms for activating lytic gene expression have received much attention, how RTA impacts cellular function is less well understood. To address this, we developed a cell line with doxycycline-inducible RTA expression and applied stable isotope labeling of amino acids in cell culture (SILAC)-based quantitative proteomics. Using this methodology, we have identified a novel cellular protein (AT-rich interacting domain containing 3B [ARID3B]) whose expression was enhanced by RTA and that relocalized to replication compartments upon lytic reactivation. We also show that small interfering RNA (siRNA) knockdown or overexpression of ARID3B led to an enhancement or inhibition of lytic reactivation, respectively. Furthermore, DNA affinity and chromatin immunoprecipitation assays demonstrated that ARID3B specifically interacts with A/T-rich elements in the KSHV origin of lytic replication (oriLyt), and this was dependent on lytic cycle reactivation. Therefore, we have identified a novel cellular protein whose expression is enhanced by KSHV RTA with the ability to inhibit KSHV reactivation.

LanguageEnglish
Pages9543-9555
Number of pages13
JournalJournal of Virology
Volume90
Issue number20
Early online date10 Aug 2016
DOIs
Publication statusPublished - 29 Sep 2016
Externally publishedYes

Fingerprint

Human herpesvirus 8
Human Herpesvirus 8
transcription (genetics)
Kaposi's Sarcoma
sarcoma
Primary Effusion Lymphoma
Virus Latency
Isotope Labeling
immunocompromised population
isotope labeling
Proteins
Replication Origin
doxycycline
Doxycycline
Chromatin Immunoprecipitation
Herpesviridae
viral proteins
Viral Proteins
small interfering RNA
Life Cycle Stages

Cite this

Wood, J. J., Boyne, J. R., Paulus, C., Jackson, B. R., Nevels, M. M., Whitehouse, A., & Hughes, D. J. (2016). ARID3B: A novel regulator of the Kaposi's sarcoma-associated herpesvirus lytic cycle. Journal of Virology, 90(20), 9543-9555. https://doi.org/10.1128/JVI.03262-15
Wood, Jennifer J. ; Boyne, James R. ; Paulus, Christina ; Jackson, Brian R. ; Nevels, Michael M. ; Whitehouse, Adrian ; Hughes, David J. / ARID3B : A novel regulator of the Kaposi's sarcoma-associated herpesvirus lytic cycle. In: Journal of Virology. 2016 ; Vol. 90, No. 20. pp. 9543-9555.
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Wood, JJ, Boyne, JR, Paulus, C, Jackson, BR, Nevels, MM, Whitehouse, A & Hughes, DJ 2016, 'ARID3B: A novel regulator of the Kaposi's sarcoma-associated herpesvirus lytic cycle', Journal of Virology, vol. 90, no. 20, pp. 9543-9555. https://doi.org/10.1128/JVI.03262-15

ARID3B : A novel regulator of the Kaposi's sarcoma-associated herpesvirus lytic cycle. / Wood, Jennifer J.; Boyne, James R.; Paulus, Christina; Jackson, Brian R.; Nevels, Michael M.; Whitehouse, Adrian; Hughes, David J.

In: Journal of Virology, Vol. 90, No. 20, 29.09.2016, p. 9543-9555.

Research output: Contribution to journalArticle

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AU - Wood, Jennifer J.

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AU - Paulus, Christina

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AU - Hughes, David J.

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