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Brett Lindenbach
Assistant Professor
Microbial Pathogenesis
Ph.D. Washington University 1999
e-mail: brett.lindenbach@yale.edu
phone: (203) 785-4705 |
Research Interests:
Over 170 million people are infected with hepatitis C virus (HCV), an enveloped, positive strand RNA virus in the family Flaviviridae. HCV causes chronic liver disease that frequently leads to cirrhosis, liver failure, and cancer. A major obstacle to studying HCV has been the inability to grow the virus in the laboratory. We recently developed a reverse genetic system for producing infectious HCV in cell culture starting from cloned cDNA, and are applying a variety of genetic and biochemical approaches to examine previously inaccessible aspects of the virus life cycle.
In characterizing the physical properties of the virion, we found that infectious HCV particles exhibit an unusually low buoyant density for an enveloped RNA virus, around 1.10 g/ml. Virions with low infectivity and higher buoyant density are also formed, suggesting that viral infectivity depends on physical association with low-density serum factors. To elucidate these interactions, we are dissecting the composition and structure of purified virus particles. In addition, we are examining the cellular pathway of virion assembly, and asking whether these two virion forms exhibit differences in viral entry. In parallel studies, we are analyzing the genetic determinants of HCV RNA replication and virion assembly.
Other positive strand RNA viruses of experimental interest within the lab include other members of the Flaviviridae, including yellow fever, dengue, and West Nile viruses, as well as Flock House virus, an insect nodavirus that has proven to be a powerful tool for examining host-pathogen interactions.
Selected References
Lindenbach BD, Meuleman P, Ploss A, Vanwolleghem T, Syder AJ, McKeating JA, Lanford RE, Feinstone SM, Major ME, Leroux-Roels G, Rice CM. (2006). Cell culture-grown hepatitis C virus is infectious in vivo and can be recultured in vitro. Proc. Natl. Acad. Sci. USA, 103, 3805-3809. PDF
Lindenbach BD, Evans MJ, Syder AJ, Wolk B, Tellinghuisen TL, Liu CC, Maruyama T, Hynes RO, Burton DR, McKeating JA, Rice CM. (2005). Complete replication of hepatitis C virus in cell culture. Science 308, 623-626. PDF
Lindenbach BD, Rice CM. Unravelling hepatitis C virus replication from genome to function. (2005). Nature 436, 933-938. PDF
Lindenbach BD, Thiel HJ, Rice CM. Flaviviridae: the viruses and their replication. In: Fields Virology. 5th Edition. DM Knipe, PM Howley, Eds. Philadelphia: Lippincott-Raven Publishers. PDF
Click here for the infectivity calculator (1/20/08)
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