Gail W. Wertz

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Research Interest(s)

Molecular Virology, Transcriptional Control, Viral Vaccine Development

Research Description

Lab Research Focus
RNA viruses are among the most serious uncontrolled causes of extant and emerging infectious disease. The Wertz lab investigates the molecular mechanisms of replication and transcription of the non-segmented negative strand RNA viruses. Using the prototypic rhabdovirus, VSV, and the major childhood pathogen, human respiratory syncytial virus, HRSV, we investigate the cis-acting signals and trans-acting factors involved in control of gene expression and genome replication of these viruses to understand at the molecular level how these agents replicate, cause disease and may be controlled. These viruses have an elegantly simple mechanism for controlling gene expression, which is by the highly conserved order of their genes relative to a single transcriptional promoter. We have used this principle for control of transcription to manipulate the phenotype by rearranging the order of genes. By translocation of individual genes, or groups of genes to up or down regulate their levels of expression, we have developed stable virus variants that allow investigation of the role of these gene products in numerous aspects of the virus replication cycle and the interaction of the virus with its host. In the case of HRSV we have found that in addition to antigenic variation to evade an existing immune response, genetic variation exists in transcriptional signals of clinical lineages which can alter control of expression of important genes and affect reinfection potential. We are currently analyzing the stability and evolution of viruses with changes introduced into control elements and using the power of selective pressure to identify key cis- and trans-acting elements in the processes of transcription and replication.