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Proteasome inhibitor MG132 blocks viral DNA replication and assembly of human cytomegalovirus
Author(s) -
Kaspari Marion,
Tavalai Nina,
Stamminger Thomas,
Zimmermann Albert,
Schilf Rita,
Bogner Elke
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.01.040
Subject(s) - mg132 , proteasome inhibitor , human cytomegalovirus , proteasome , microbiology and biotechnology , dna replication , biology , viral replication , virology , chemistry , dna , virus , biochemistry
This study provides evidence that proteasomal activity is required at multiple steps in human cytomegalovirus replication. Electron microscopy revealed that no viral particles were assembled in the presence of proteasome inhibitor MG132. Immunofluorescence and Western blot analyses using MG132 demonstrated that immediate early gene expression was suppressed at low but not high MOI. In contrast, expression of late proteins was completely blocked independent of MOI. Additionally, pulsed‐field gel electrophoresis demonstrated that MG132 interferes with cleavage of HCMV DNA. Bromodeoxyuridine incorporation studies showed that de novo viral DNA synthesis is reduced in the presence of MG132. Furthermore, in contrast to previous hypotheses we demonstrated that neither the ND10 components PML and hDaxx nor NFκB activation represent the target for MG132.