Determining the requirement for viral DNA amplification in mediating the reorganization of cellular chromatin during the Epstein-Barr virus lytic cycle
Abstract
We have uncovered how Epstein-Barr virus (EBV) induces the reorganization of cellular chromatin
(ROCC), where host chromatin is compacted and marginated within the nucleus. We tested the role of
EBV lytic DNA amplification in driving ROCC and learned that inhibiting it supports chromatin
compaction but blocks margination. We favor two steps for EBV’s ROCC: EBV first mediates a cellular
response leading to global chromatin compaction, and second, viral DNA synthesis drives margination of
cellular DNA. We asked if the histone-associated simian virus 40 (SV40) DNA synthesis could substitute
for EBV’s histone-free viral DNA synthesis and found that EBV’s ROCC is incompatible with SV40
DNA replication. We conclude that, during its lytic phase, EBV blocks DNA synthesis in which
histones are loaded onto newly synthesized DNA, in favor of its own histone-free lytic DNA
amplification.
Permanent Link
http://digital.library.wisc.edu/1793/84964Type
Thesis