Functional genomics in virology and antiviral drug discovery

DeFilippis, Victor R.; Raggo, Camilo; Moses, Ashlee V.; Früh, Klaus

doi:10.1016/s0167-7799(03)00207-5

Cited by 32 publications

(24 citation statements)

References 53 publications

(54 reference statements)

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“…Because siRNA treatment results in the specific destruction of a target mRNA, proof for its effective action can be obtained on the RNA level. To verify that RNA interference was able to inhibit gene expression as well as transformation of DMVEC, we first examined the effect of siRNA against c-Kit using the same techniques (immunostaining to verify inhibition of protein expression; post-confluent growth and phenotype in the focus inhibition assay) successfully established for Kit-PMO-AS treatment (30). siRNA against c-Kit inhibited both c-Kit protein expression and focus formation (30).…”

Section: Inhibition Of Foci Formation Inmentioning

confidence: 99%

“…To verify that RNA interference was able to inhibit gene expression as well as transformation of DMVEC, we first examined the effect of siRNA against c-Kit using the same techniques (immunostaining to verify inhibition of protein expression; post-confluent growth and phenotype in the focus inhibition assay) successfully established for Kit-PMO-AS treatment (30). siRNA against c-Kit inhibited both c-Kit protein expression and focus formation (30). Thus, we obtained siRNAs specific for RDC1 and Neuritin and did qRT-PCR on siRNA-transfected KSHV-DMVEC to examine if siRNA treatment reduced the levels of RDC1 and Neuritin mRNA.…”

Section: Inhibition Of Foci Formation Inmentioning

confidence: 99%

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Novel Cellular Genes Essential for Transformation of Endothelial Cells by Kaposi's Sarcoma–Associated Herpesvirus

et al. 2005

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Kaposi's sarcoma-associated herpesvirus (KSHV) is involved in the development of lymphoproliferative diseases and Kaposi's sarcoma. The oncogenicity of this virus is reflected in vitro by its ability to transform B cells and endothelial cells. Infection of dermal microvascular endothelial cells (DMVEC) transforms the cells from a cobblestone-like monolayer to foci-forming spindle cells. This transformation is accompanied by dramatic changes in the cellular transcriptome. Known oncogenes, such as c-Kit, are among the KSHV-induced host genes. We previously showed that c-Kit is an essential cellular component of the KSHV-mediated transformation of DMVEC. Here, we test the hypothesis that the transformation process can be used to discover novel oncogenes. When expression of a panel of KSHV-induced cellular transcripts was inhibited with antisense oligomers, we observed inhibition of DMVEC proliferation and foci formation using antisense molecules to RDC1 and Neuritin. We further showed that transformation of KSHV-infected DMVEC was inhibited by small interfering RNA directed at RDC1 or Neuritin. Ectopic expression of Neuritin in NIH 3T3 cells resulted in changes in cell morphology and anchorage-independent growth, whereas RDC1 ectopic expression significantly increased cell proliferation. In addition, both RDC1-and Neuritin-expressing cells formed tumors in nude mice. RDC1 is an orphan G proteincoupled receptor, whereas Neuritin is a growth-promoting protein known to mediate neurite outgrowth. Neither gene has been previously implicated in tumorigenesis. Our data suggest that KSHV-mediated transformation involves exploitation of the hitherto unrealized oncogenic properties of RDC1 and Neuritin. (Cancer Res 2005; 65(12): 5084-95)

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Section: Inhibition Of Foci Formation Inmentioning

confidence: 99%

Section: Inhibition Of Foci Formation Inmentioning

confidence: 99%

Novel Cellular Genes Essential for Transformation of Endothelial Cells by Kaposi's Sarcoma–Associated Herpesvirus

et al. 2005

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“…Through the unraveling of discoveries made by viruses, a new class of therapeutic agents has been revealed based upon virus-engineered immunomodulatory proteins. Viruses were the first organisms for which complete genome sequences were deduced, beginning a quarter of a century ago, and the science of "virogenomics" has been expanding rapidly ever since (177)(178)(179). The repertoire of novel viral gene products that are devoted to host modulation has also been proliferating at an astounding rate, and there are reasons to suspect that we have uncovered only the tip of the virus iceberg.…”

Section: Future Prospectsmentioning

confidence: 99%

Secreted Immunomodulatory Viral Proteins as Novel Biotherapeutics

Lucas

McFadden

2004

The Journal of Immunology

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Many viruses have learned to evade or subvert the host antiviral immune responses by encoding and expressing immunomodulatory proteins that protect the virus from attack by elements of the innate and acquired immune systems. Some of these viral anti-immune regulators are expressed as secreted proteins that engage specific host immune targets in the extracellular environment, where they exhibit potent anti-immune properties. We review here viral immunomodulatory proteins that have been tested as anti-inflammatory reagents in animal models of disease caused by excessive inflammation or hyperactivated immune pathways. The potential for such viral molecules for the development of novel drugs to treat immune-based or inflammatory disorders is discussed.

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“…The uses of DNA microarray technology in virology have been reviewed [20][21][22][23][24]. Its potential benefits are able to provide a better understanding of the viral DNA replication and gene expression strategies; identify viral gene functions; provide possible clues for the pathogenesis of the virus, and provide insights into the complex host-virus interactions.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional profile of red seabream iridovirus in a fish model as revealed by viral DNA microarrays

et al. 2007

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Red seabream iridovirus (RSIV) disease is a serious disease of many marine fish species in Japan and elsewhere. For a better understanding of the molecular pathogenic mechanism, we examined the transcriptional profile of RSIV in infected fish using a DNA microarray. Expression of RSIV open reading frames (ORFs) was first detected at about 5 days post-infection (d.p.i.), and accounted for about 45% of total ORFs. Almost all the ORFs (97-99%) were expressed at their maximum levels during 7-9 d.p.i. The expression levels and the number of expressed ORFs started to decrease at 10 d.p.i. These results suggest that pathogenesis of RSIV infection began at around day 5, and continued with high levels of viral multiplication until viral clearance by host antiviral defenses starting from around 10 d.p.i. A comparison of viral gene expressions in the spleen and kidney over the course of the infection suggests that RSIV preferentially targets the spleen. The spleen may thus be the most susceptible organ for diagnosis of iridoviral disease.

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Functional genomics in virology and antiviral drug discovery

Cited by 32 publications

References 53 publications

Novel Cellular Genes Essential for Transformation of Endothelial Cells by Kaposi's Sarcoma–Associated Herpesvirus

Novel Cellular Genes Essential for Transformation of Endothelial Cells by Kaposi's Sarcoma–Associated Herpesvirus

Secreted Immunomodulatory Viral Proteins as Novel Biotherapeutics

Transcriptional profile of red seabream iridovirus in a fish model as revealed by viral DNA microarrays

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