Bates Laboratory for the study of Host:Viral interactions                                             Perelman School of Medicine at the University of Pennsylvania

 

 

 

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Research


Ebolavirus-host cell interactions


Forward genetic screens in human haploid cells


Analysis of the cell-intrinsic immune factor tetherin


 

Forward genetic screens in human haploid cells

Interrogation of insertionally mutagenized haploid cells is a powerful technology to identify genes important for a specific function. The recent availability of haploid mammalian cells makes possible the use of this technology to identify host factors that interact with viruses and promote infection. We have developed a gene-trap lentiviral vector that act as an insertional mutagen and produced a library of >200 million haploid human cells bearing insertions.  We are interrogating this library by employing novel replication-competent, recombinant vesicular stomatitis viruses bearing on their surface various viral glycoproteins.  Cells resistant to infection by these recombinant viruses contain inactivating mutations in host factors needed for infection that can be readily identified using massively parallel deep sequencing technology. 

Currently our focus is on members of the Bunyaviridae family.  Bunyaviruses include within the >300 known family members many important human pathogens such as Crimean Congo Hemorrhagic Fever Virus, Hantaan Virus, Rift Valley Fever Virus, and Sin Nombre Virus.  Although many bunyaviruses are arthropod borne, others are spread by aerosolized rodent excreta. A variety of pathologies result from infection by different bunyaviruses including hemorrhagic fever with renal syndrome (HFRS) which is caused by viruses found in Europe and Asia or hantavirus pulmonary syndrome (HPS) caused by the “new world” viruses of the Americas. Other bunyaviruses cause potentially severe encephalitis. Despite the pathogenic nature of many bunyaviruses and their widespread distribution, which makes human infection relatively common, there are no US licensed vaccines or effective therapies currently available for them. Indeed research on these viruses has been hampered by their high pathogenicity. For this research program we have developed non-pathogenic recombinant viruses that rely upon the glycoproteins of highly pathogenic bunyaviruses for infection thereby permitting analysis under low containment conditions.  The understanding of host factors and pathways important for bunyavirus infection that will result from the proposed research will contribute greatly to our basic knowledge about the biology of infection by these agents. Additionally, our findings should lay the groundwork for identification of agents that impair the entry mechanisms of these viruses and may help in development of therapeutics for these highly pathogenic infections.

 

News & Events

 


01.30.14

Ken finally updates website!!


01.30.14

Press release for MJ & Ken's paper!!


12.18.13

MJ & Ken's paper published in PLoS Pathogens!!


06.07.13

Ben Dyer joins the lab for his thesis work! Did I mention he also received an NSF award?! Go Ben!!


05.31.13

MJ Drake completes her prelim exam!


05.16.13

Alexa Nicolas graduates Penn & completes her thesis work!


05.4.13

Ken Briley presents a poster at the 2013 Viruses & Cells Gordon Conference....in Italia!


09.27.12

Luis Cocka publishes his Tetherin work in PLoS Pathogens!


 


 

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