Transcriptional Coactivators Not Useful As Herpes Antiviral Drug Targets

Researchers sought to determine how herpes simplex virus “turns on” its viral genes during the first stages of infection. Specifically, they tested whether the expression of the viral genes would be similar to how cellular genes are turned on, and specifically whether the viral genes would depend on a set of cellular proteins called “coactivators.”

“Based on an earlier model we expected that expression of the viral genes would depend on a set of transcriptional coactivators,” said Scientific Investigator Steve Triezenberg, Ph.D., head of the VARI Laboratory of Transcriptional Regulation and co-author of the study published in a recent issue of the Journal of Virology. “As it turns out, we got an unexpected answer.  Using several different approaches, we consistently saw that the coactivator proteins are not required for viral gene expression.”

Researchers have understood that virion protein 16 (VP16) of herpes simplex virus type 1 is a potent transcriptional activator of viral immediate early (IE) genes. However, the role of transcriptional coactivators had not been fully understood.

“This is a significant finding because it tells us that chemical inhibitors of these coactivators are not likely to be good antiviral drugs, despite our earlier model,” said Triezenberg.