Inhibitory effect of hexamethylene bisacetamide on replication of human cytomegalovirus

Abstract

The effect of hexamethylane bisacetamide (HMBA), a hybrid polar compound, on gene expression and replication of human cytomegalovirus (HCMV) was studied. When HCMV-infected human thyroid papillary carcinoma (TPC-1) and human embryonic lung (HEL) fibroblast cells were maintained with medium containing 2.5 and 5 mM HMBA for 10 days, there was a greater than 2- to 3-log reduction in virus yield compared to that in untreated cells. Infection of TPC-1 cells with HCMV resulted in an establishment of persistent infection and the cells continuously produced virus with titer of over 10(5) PFU/ml, whereas HMBA prevented the infected cells from entering into the persistent infection. Moreover, treatment of the persistently infected cultures with HMBA reduced production of infectious HCMV more efficiently than did ganciclovir, and eventually ceased HCMV production. Western blotting analysis revealed that HMBA blocks accumulation of the immediate early 2 (IE2) protein in TPC-1 cells and delays synthesis of this protein in HEL cells, but has little effect on the level of the IE1 protein during the early times after infection. Synthesis of the viral early and late proteins in both cells was also substantially blocked by HMBA. The results indicate that the inhibition or the delay of the critical IE2 protein synthesis in the presence of HMBA would actually be a process that fails to proceed beyond the IE stages in HCMV replication cycle.

Hexamethylene bisacetamide leads to reduced helper virus‐free HSV‐1 amplicon expression titers via suppression of ICP0

“…The differentiation-related effect of HMBA has not been demonstrated directly in BHK-or Vero-derived cell lines, which are commonly used to package HSV amplicon vectors, but such a mechanism of action could significantly alter viral and cellular protein profiles and metabolism, thereby influencing expression and transduced vector genome titers. In fact, HMBA has been shown to impart an inhibitory effect on human cytomegalovirus (CMV) replication via blocking the accumulation of the immediate-early 2 (IE2) protein [48]. Our data suggest that HMBA does not impinge on the replication of the HSV-1 amplicon plasmid in packaging cells, as genome-containing amplicon particle numbers (transduced vector genome titers) were unaffected whether stocks were packaged in the presence or absence of 2 mM HMBA (Figures 1 and 2).…”