Neal A. DeLuca, PhD

Repression and activation of persisting HSV genomes: Herpes simplex virus can undergo either a productive infection, where all the viral genes are expressed culminating in the production of progeny virus and cell death, or it can enter a latent state, which is characterized by the relative lack of viral gene expression, genome persistence, and cell survival.  The latent state typically occurs only in neurons, and may involve the attenuation of immediate early (IE) gene expression, and thus the lack of later viral gene expression.  We study the expression and state of quiescent persisting HSV genomes ChIP, RT-PCR, ChIP-seq, and RNA-seq techniques.  We have found that quiescent genomes are largely repressed and exist in multiple states that differ with respect to nucleosome packaging, histone acetylation and methylation, and heterochromatin formation.  The result is a stochastic mix of epigenetic states that differ with respect to gene expression.  We also study the ability and mechanisms of action of viral activator proteins to overcome these repressive states, resulting in reactivation.

Virus-cell interactions affecting HSV gene expression:  In its productive life cycle, the genes of HSV are expressed in a sequential manner, with those controlling subsequent gene expression produced very early in infection.  One of these, ICP4, is required for productive virus infection because it activates the expression of the remaining 80 or so early and late genes.  ICP4 activates early and late genes by different mechanisms involving different interactions with TFIID, mediator, and other cellular transcription factors.  To study these mechanisms, we examine the association of ICP4 and cellular transcription complexes on HSV promoters during infection by ChIP and mass spectrometry. The regions of ICP4 that are important for these interactions are determined, and the effects of these interactions on the transcription and hence expression of different classes of HSV genes is examined.  In addition, we have discovered that there are regions of ICP4 that are not required for productive viral growth in non-neuronal cells, but are absolutely required for function in neurons of the trigeminal ganglia, the site where HSV establishes latency.  The basis for this requirement is current under study.

Lab Personnel

Jill Dembowski – Postdoc
Muhamuda Kadar, PhD - Postdoc
Justine Harkness - Graduate Student
Soumya Nanda - Graduate Student
Fran Sivrich - Research Technician

Areas of Interest

Regulation of Viral Gene Expression; Mechanisms of Viral Persistence.