Post-translational Modification of a Key Transcription Factor for HSV-1 Infection

Student Author(s)

Jamie Gritt

Faculty Mentor(s)

Dr. Steve Triezenberg

Document Type


Event Date



Herpes simplex virus type 1 (HSV-1) is a highly prevalent virus that causes cold sores. The HSV-1 virion contains VP16, an important multifunctional protein. VP16 is a potent transcriptional activator that recruits host cell proteins, including Oct-1, to initiate immediate early (IE) viral gene expression and therefore the lytic cycle. The VP16 amino acid residue serine 375 resides in a consensus casein kinase II (CKII) site and lies within the region which interacts with Oct-1. We hypothesize that phosphorylation by CKII at serine 375 upon infection activates VP16 to initiate complex formation with Oct-1 and induce IE gene expression. Pharmacological inhibition of CKII with TBCA resulted in an 80% decrease in IE mRNA levels at 2 hours post infection (hpi) as quantified using qRTPCR. However, phosphorylation at serine 375 could not be detected in infected cell lysates 2-8 hpi using western blotting. In contrast, significant phosphorylation at serine 375 was detected at 20 hpi. Preliminary data suggests that phosphorylated VP16 may be preferentially packaged into the tegument of infectious virions. These data support an alternative mechanism by which late synthesized VP16 is phosphorylated at serine 375, packaged into infectious virions and delivered to the next cell pre-modified for Oct-1 complex formation and IE transcription activation.


Research conducted at Laboratory of Transcriptional Regulation, Van Andel Institute

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