2,3,7,8-Tetrachlorodibenzo-p-dioxin influences bovine herpesvirus 1 replication through upregulation of SIRT3 and cytoskeletal reorganization

Abstract

Infection of kidney cells (MDBK) with Bovine Herpesvirus 1 (BoHV-1) is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which accelerates BoHV-1-induced apoptosis and increases virus replication. Herein, to elucidate the mechanism through TCDD modifies BoHV-1 infection, we analyzed the modulation of a members of Sirtuin proteins family in MDBK cells. We found that mitochondrial SIRT3 was upregulated during infection. This change was accompanied by cytoskeletal rearrangements and cell extensions. All these trends were drastically modified by TCDD. We hypothesize that, taken together, these results might further clarify the processes responsible for the action of TCDD on the BoHV-1 replication, resulting in enhanced virus production.

Membrane Currents in Madin-Darby Bovine Kidney Cells are Enhanced by Exposure to Dioxin

“…TCDD (Supelco, 48599) was initially diluted to give a 10, 000pg/ml stock solution by mixing with DMEM. This stock solution was then diluted to give a working solution of 1pg/ml in DMEM, which was added to cultures [4,[19][20][21][22][23][24][25]30].…”

“…In human SH-SY5Y neuronal cell line, Morales-Hernandez et al [15] have related TCDD toxicity to a disruption of calcium homeostasis while others [16][17][18] have established that the Aryl Hydrocarbon Receptor (AhR), to which TCDD binds with a high affinity, is involved in mediating the diverse toxic responses of this dioxin. In Madin-Darby Bovine Kidney (MDBK), an epithelial cell line, through AhR [19,20], TCDD induced a significant cell proliferation [21], increased the incidence cell death with autophagy [19,20,22] and promoted the Bovine Herpesvirus-1 (BoHV-1) infection as well as BoHV-1-induced apoptosis [4,[19][20][21][23][24][25].…”

“…The membrane elec-trical activity is due to the influx/efflux of ions across ion channels and pumps. It regulates the homeosta-sis of the cell [27] and many fundamental processes like as autophagy [28] and apoptosis [29] that also result to be very sensitive to TCDD [4,[19][20][21][22][23][24][25].…”

“…In the present study we used MDBK, a cell line affected by TCDD as defined by our previous studies [4,[19][20][21][22][23][24][25]. By using a patchclamp technique in the whole cell configuration, we have tested the possibility that the effect of this chemical can alter the normal ionic membrane currents.…”

DNA Damage Response Differentially Affects BoHV-1 Gene Transcription in Cell Type-Dependent Manners

“…As a nuclear replicating virus, BoHV-1 infection induces oxidative DNA damage in multiple cell cultures, such as bovine kidney cells (MDBK) and human A549 lung carcinoma epithelial cells, as demonstrated by the increased production of DSBs analyzed by comet assay [ 10 , 13 , 14 ]. Accumulating studies have indicated that damaged DNA can activate various cell death pathways [ 13 ], and BoHV-1infection induces diverse forms of cell death both in vivo and in vitro [ 14 , 15 , 16 , 17 , 18 , 19 ], which underscores the implication of virus-infection-induced DNA damage in the virus pathogenesis. In addition, as an oncolytic virus, BoHV-1 infection in human lung adenocarcinoma cells A549 results in cell lesions partially by inducing DNA damage [ 10 ], which underlies the importance of DNA damage in the virus oncolytic effects.…”