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Recently, research groups at the University of California San Francisco (UCSF) developed a DNA microarray with the potential to detect all known as well as unknown viruses (Wang et al., 2003). The design of the array is based on the most conserved regions within each viral family. In total, the array contains more than 22000 70mer sequences (all viral genomes represented in the NCBI database at 2004, 30 bacterial genomes and human control genes). During her postdoctoral studies Dr. Nicole Fischer worked together with bioinformatics specialists and clinicians at UCSF to apply this technique to find novel viruses. Using this array we were able to identify a novel xenotropic gammaretrovirus associated with a rare form of prostate cancer (Fischer, Urisman, Molinaro et al., 2006).
We use this array to search for novel viruses in acute infectious syndromes, chronic diseases and human cancer.
Blow up of one sector (out of 42) of the Virochip. Viral signals are labelled in red, a random 70mer hybridizing to all sequences on the array is shown in green.
In addition to hunt for novel viruses our group is interested in developing this technique as a putative diagnostic tool. At date, we are designing a respiratory viral and bacterial microarray to detect viruses in acute respiratory infections and pneumonia. 2000 oligonucleotide sequences of conserved regions as well as species specific regions of the most common viral and bacterial respiratory pathogens are spotted on polylysine coated glass slides. Experiments comparing the performance of this respiratory array to the commonly used multiplex PCR are currently under investigations.
XMRV, a xenotropic murine leukemia virus related gammaretrovirus recently discovered in a rare form of human prostate cancer, is the first bonafide human infection with a xenotropic murine leukemia virus. The virus was found to infect prostatic stroma cells with low frequency (0.5-1.2%) in patients homozygous for a missense mutation in the RNASEL gene, R462Q (Fischer, Urisman, Molinaro, et al., 2006). RNASEL an endoribonuclease of the antiviral defense pathway was one of the first prostate cancer susceptibility genes discovered. The implication of a viral infection in the development of prostatic cancer has been discussed for years although no data revealing a causative connection of viral infections and tumorigenesis in the prostate exist.
Our lab is interested in the role of XMRV in tumorigenesis and in cellular defense mechanisms against XMRV infection.
Fluorescence in situ hybridization using XMRV as a probe in prostate cancer tissue: infected cells are shown in green (SyBr-Green), epithelial cells are stained with a monoclonal antibody against cytokeratin.
Our lab is interested in epidemiological questions ons with regard to seroprevalence of XMRV infection, transmission of XMRV and clearance of viral infection.
To succeed in this task the focus of our lab is to develop a blood test allowing high throughput screening of human sera.
Murine leukemia viruses (MLV) are divided into subgroups depending on their host range. Ecotropic viruses (MoMuLV, Friend MuLV, Rauscher MuLV) infect only mice cells using the cationic amino acid transporter protein mCAT-1 as a receptor. Amphotropic viruses are able to infect species different from mice (including human) as well as mice. Here, the receptors used are sodium dependent phosphate transporters called PIT1 and PIT2. Xenotropic viruses infect some wild type mice and species different from mice (including human). The receptor identified for xenotropic viruses is a transmembrane protein called Xpr1 (Syg1). All these different MuLV classes have related but distinct envelope antigens responsible for receptor recognition. Specific domains within the env proteins are responsible for receptor recognition and binding.
Our lab is studying the receptor usage of the recently identified gammaretrovirus XMRV in human and mouse cells, characterizing regions within the env protein responsible for receptor binding and identifying additional cellular proteins involved in XMRV entry.
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Group Fischer |
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