Chromatin immunoprecipitation and microarray analysis suggest functional cooperation between Kaposi's Sarcoma-associated herpesvirus ORF57 and K-bZIP.

Abstract:

:The Kaposi's sarcoma-associated herpesvirus (KSHV) open reading frame 57 (ORF57)-encoded protein (Mta) is a multifunctional regulator of viral gene expression. ORF57 is essential for viral replication, so elucidation of its molecular mechanisms is important for understanding KSHV infection. ORF57 has been implicated in nearly every aspect of viral gene expression, including transcription, RNA stability, splicing, export, and translation. Here we demonstrate that ORF57 interacts with the KSHV K-bZIP protein in vitro and in cell extracts from lytically reactivated infected cells. To further test the biological relevance of the interaction, we performed a chromatin immunoprecipitation and microarray (ChIP-chip) analysis using anti-ORF57 antibodies and a KSHV tiling array. The results revealed four specific areas of enrichment, including the ORF4 and K8 (K-bZIP) promoters, as well as oriLyt, all of which interact with K-bZIP. In addition, ORF57 associated with DNA corresponding to the PAN RNA transcribed region, a known posttranscriptional target of ORF57. All of the peaks were RNase insensitive, demonstrating that ORF57 association with the viral genome is unlikely to be mediated exclusively by an RNA tether. Our data demonstrate that ORF57 associates with the viral genome by using at least two modes of recruitment, and they suggest that ORF57 and K-bZIP coregulate viral gene expression during lytic infection.

journal_name

J Virol

journal_title

Journal of virology

authors

Hunter OV,Sei E,Richardson RB,Conrad NK

doi

10.1128/JVI.03459-12

subject

Has Abstract

pub_date

2013-04-01 00:00:00

pages

4005-16

issue

7

eissn

0022-538X

issn

1098-5514

pii

JVI.03459-12

journal_volume

87

pub_type

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