Prolonged activation of NF-kappaB by human cytomegalovirus promotes efficient viral replication and late gene expression.
Infection of fibroblasts by human cytomegalovirus (HCMV) rapidly activates the NF-kappaB signaling pathway, which we documented promotes efficient transactivation of the major immediate-early promoter (DeMeritt, I.B., Milford, L.E., Yurochko, A.D. (2004). Activation of the NF-kappaB pathway in human cytomegalovirus-infected cells is necessary for efficient transactivation of the major immediate-early promoter. J. Virol. 78, 4498-4507). Because a second, sustained increase in NF-kappaB activity following the initial phase of NF-kappaB activation was also observed, we investigated the role that this prolonged NF-kappaB activation played in viral replication and late gene expression. We first investigated HCMV replication in cells in which NF-kappaB activation was blocked by pretreatment with NF-kappaB inhibitors: HCMV replication was significantly decreased in these cultures. A decrease in replication was also observed when NF-kappaB was inhibited up to 48 h post-infection, suggesting a previously unidentified role for NF-kappaB in the regulation of the later class of viral genes.
DeMeritt
Ian B
IB
Department of Microbiology and Immunology and Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130-3932, USA.
Podduturi
Jagat P
JP
Tilley
A Michael
AM
Nogalski
Maciej T
MT
Yurochko
Andrew D
AD
D001241:Aspirin / Q000494:pharmacology; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000378:metabolism / Q000472:pathogenicity / Q000502:physiology*; D005347:Fibroblasts; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D007976:Leupeptins; D016328:NF-kappa B; D014764:Viral Proteins; D001241:Aspirin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde