Neal A. DeLuca, PhD

Neal A. DeLuca, PhD

Contact

514 Bridgeside Point 2
450 Technology Drive
Pittsburgh, PA 15219

Ph: 412-648-9947

Fax: 412-624-1401

ndeluca@pitt.edu

My Website »

Education

  • PhD in Biophysics, Pennsylvania State University
  • MS in Biophysics, Pennsylvania State University
  • BS in Fundamental Sciences, Lehigh University

Academic Affiliation

Professor, Department of Microbiology and Molecular Genetics

Member, Graduate Program in Microbiology and Immunology (PMI)

Member, Molecular Genetics and Developmental Biology Graduate Program

About Research

The pathogenic and cytotoxic effects of viruses are largely due to the expression of viral gene products. The hallmark of herpes simplex virus gene expression is the sequential and coordinately regulated expression of the approximately 80 viral genes. Two viral proteins, VP16 and ICP4, function to activate transcription of the five immediate early genes, and the remainder of the HSV genome, respectively. ICP4 is a large and structurally complex molecule. We study the mechanisms by which the major regulatory protein of HSV, ICP4, affects the pol II transcriptional apparatus of the cell resulting in the regulation of HSV genes.
In addition to the modification of polII transcription by ICP4, many other cellular nuclear processes are modified by viral gene products to support productive infection.  Many of these processes function on the viral genome.  The viral genome is the only component of the virus present throughout its productive life cycle. We have developed approaches to determine in a nonbiased way, the viral and cellular proteins that associate with the genome throughout infection, from the initial sensing of the genome to its packaging, and to image these genomes relative to cellular structures and proteins.
HSV gene expression during lytic infection is contrasted by the ability to establish latency in PNS neurons. During latency, viral lytic gene expression does not occur, and the genome persists as an episomal element packaged in chromatin. The use of mutants deficient in subsets of the IE proteins provides the means to examine viral gene expression and genome persistence in the absence of lytic gene expression in tissue culture. Mutants that do not express any of the five IE proteins establish a long-term relationship with the cell. Gene expression from the persisting genomes is repressed by repressive chromatin, and interferon signaling is induced. Both processes can be reversed by the addition of ICP0. We study the interplay between genome repression, activation, and the cellular antiviral response.

Selected Publications

Fox HL, Dembowski JA, and DeLuca NA. 2017. A herpesviral immediate early protein promotes transcription elongation of viral transcripts. mBio. e00745-17. doi: 10.1128/mBio.00745-17.

Dembowski JA, Dremel SE, and DeLuca N. 2017. Replication-Coupled Recruitment of Viral and Cellular Factors to Herpes Simplex Virus Type 1 Replication Forks for the Maintenance and Expression of Viral Genomes. PLOS Pathog. 13: e1006166.

Dembowski JA and DeLuca NA. 2015. Selective recruitment of nuclear factors to productively replicating herpes simplex virus genomes. PLoS Pathog. 11: e1004939.

Harkness JM, Kader M and DeLuca NA. 2014. Transcription of the Herpes Simplex Virus 1 Genome during Productive and Quiescent Infection of Neuronal and Nonneuronal Cells. J. Virol. 88: 6847-6861.

Wagner LM and DeLuca NA. 2013. Temporal Association of Herpes Simplex Virus ICP4 with Cellular Complexes Functioning at Multiple Steps in PolII Transcription. PLoS One. 8: e78242.