Biomedical Sciences Graduate Program(s)
Biomedical Sciences Graduate Programs
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.
Sastre, P. A.G.Oomens and G.W. Wertz. 2007. The stability of Human Respiratory Syncytial Virus is enhanced by incorporation of the baculovirus GP64 Protein. Vaccine; In Press.
Green,T.J., X. Zhang, G.W. Wertz and M. Luo. 2006. Structure of the Vesicular Stomatitis Virus Nucleoprotein-RNA Complex. Science. 313 (5785):357-360.
Barr, J.N., J. Rogers and G.W. Wertz. 2006. Identification of the Bunyamwera bunyavirus transcription termination signal. J Gen Virol. 87:189-98.
Wertz, G. W. and R.M. Moudy. 2004. Antigenic and genetic variation in human respiratory syncytial virus. The Pediatric Infectious Disease Journal. 23:s19-24.
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