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Dustin Petrik

Mentor: Mark Stinski, Ph.D.
Lab Phone: 335-9989

In vivo analysis of human cytomegalovirus IE2 mutations using a bacterial artificial chromosome (BAC) system

Human cytomegalovirus (HCMV), a member of the betaherpesvirus group, is a ubiquitous pathogen that infects 50-100% of the world population. HCMV infection is asymptomatic in healthy individuals, but causes serious disease in immunocompromised patients and newborn children. Like other herpesviruses, HCMV has a temporal pattern of gene expression, referred to as immediate early (IE), early, and late genes. Two IE genes, designated IE1 and IE2, regulate viral early gene expression and are required for productive viral infection. IE2 is also involved in cell cycle regulation, inhibition of apoptosis, and autorepression of IE gene expression. IE1 and IE2 encode two major proteins, designated IE72 and IE86, respectively, as well as several isomers. In addition, IE2 also encodes a late protein, L40. Previously, it was difficult to construct recombinant viruses with mutations in essential genes, such as IE2. Therefore, most data regarding the function of IE1 and IE2 was acquired by transient transfection assays and in vitro binding assays. These assays have limited biological relevance because they are not in the context of the viral genome during the productive replication cycle. Using the recent bacterial artificial chromosome (BAC)-HCMV technology, we are now able to construct recombinant viruses with mutations in essential genes in bacteria and then assay the mutations in permissive human fibroblast cells. I intend to characterize the domains of the IE86 protein that are necessary for its function and determine the role of the isomers in vivo.

Stinski MF, Petrik DT. Functional roles of the human cytomegalovirus essential IE86 protein. Curr Top Microbiol Immunol. 2008;325:133-52. Review. PubMed PMID: 18637504.

Petrik DT, Schmitt KP, Stinski MF. The autoregulatory and transactivating functions of the human cytomegalovirus IE86 protein use independent mechanisms for promoter binding. J Virol. 2007 Jun;81(11):5807-18. Epub 2007 Mar 21. PubMed PMID: 17376893; PubMed Central PMCID: PMC1900308.

Petrik DT, Schmitt KP, Stinski MF. Inhibition of cellular DNA synthesis by the human cytomegalovirus IE86 protein is necessary for efficient virus replication. J Virol. 2006 Apr;80(8):3872-83. PubMed PMID: 16571804; PubMed Central PMCID:PMC1440472.

Honors and Awards

  • American Society of Microbiology, American Society for Virologists
  • Teaching: Principles of Infectious Disease Lab (Fall 2002)
  • International Herpesvirus Workshop, Madison, WI, July 2003.