%0 Journal Article
%T Chloroquine triggers Epstein-Barr virus replication through phosphorylation of KAP1/TRIM28 in Burkitt lymphoma cells
%A Eric M. Burton
%A Sumita Bhaduri-McIntosh
%A Xiaofan Li
%J -
%D 2017
%R 10.1371/journal.ppat.1006249
%X Trials to reintroduce chloroquine into regions of Africa where P. falciparum has regained susceptibility to chloroquine are underway. However, there are long-standing concerns about whether chloroquine increases lytic-replication of Epstein-Barr virus (EBV), thereby contributing to the development of endemic Burkitt lymphoma. We report that chloroquine indeed drives EBV replication by linking the DNA repair machinery to chromatin remodeling-mediated transcriptional repression. Specifically, chloroquine utilizes ataxia telangiectasia mutated (ATM) to phosphorylate the universal transcriptional corepressor Kr¨¹ppel-associated Box-associated protein 1/tripartite motif-containing protein 28 (KAP1/TRIM28) at serine 824 ¨Ca mechanism that typically facilitates repair of double-strand breaks in heterochromatin, to instead activate EBV. Notably, activation of ATM occurs in the absence of detectable DNA damage. These findings i) clarify chloroquine¡¯s effect on EBV replication, ii) should energize field investigations into the connection between chloroquine and endemic Burkitt lymphoma and iii) provide a unique context in which ATM modifies KAP1 to regulate persistence of a herpesvirus in humans
%K Chloroquine
%K Phosphorylation
%K Lytic cycle
%K DNA damage
%K Epstein-Barr virus
%K DNA replication
%K Immunoblotting
%K Viral replication
%U https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1006249