Brett David Lindenbach PhD
Associate Professor of Microbial Pathogenesis
Cell Biology; Enveloped Viruses; Hepatitis; Hepatitis C Virus; Molecular Biology; Positive-strand RNA Viruses; RNA; Virology; Virus
Hepatitis C virus (HCV) is an enveloped, positive-strand RNA virus that chronically infects over 170 million people, causing progressive liver disease that can lead to cirrhosis and hepatocellular carcinoma. We have contributed to the development of a system for growing infectious HCV in cell-culture starting from cloned cDNA, allowing us to fully dissect this pathogen at the level of genetics and biochemistry. We find that HCV infectivity correlates with virions exhibiting a low buoyant density, suggesting that infectivity depends on interaction with low-density serum components.
To understand further the molecular composition of infectious HCV particles, we are scaling up and purifying virions for proteomic and imaging analysis. These observations also suggest unique properties at the interface between HCV and its hepatocyte host. We therefore study the processes of HCV entry, RNA replication, and virion assembly at the level of cell biology. To aid in this analysis we are developing viruses with useful chemical and fluorescent tags. Other positive-strand RNA viruses of experimental interest include yellow fever virus, a relative of dengue and West Nile virus in the same family as HCV, as well as Flock House virus, a small insect virus that can replicate in yeast.
- Lindenbach BD, Rice CM. (2013) "The ins and outs of hepatitis C virus entry and assembly." Nature Reviews Microbiology. 2013 Oct;11(10):688-700.
- Luo D., Ding S.C., Vela A., Kohlway A., Lindenbach B.D., Pyle A.M. (2011). "Structural Insights into RNA Recognition by RIG-I." Cell 147(2):409-22.
- Counihan N.A., Rawlinson S.M., Lindenbach B.D. (2011) “Trafficking of Hepatitis C Virus Core Protein During Virus Particle Assembly.” PLoS Pathogens 7(10): e1002302.
- Stapleford K.A., Lindenbach B.D. (2011) “Hepatitis C virus NS2 coordinates virus particle assembly through physical interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes.” J Virol. 85(4):1706-17.
- Phan T., Kohlway A., Dimberu P., Pyle A.M., Lindenbach B.D. (2011) "The acidic domain of hepatitis C virus NS4A contributes to RNA replication and virus particle assembly." J Virol. 85(3):1193-204.
- Phan T., Beran R.K., Peters C., Lorenz I.C., Lindenbach B.D. (2009). "Hepatitis C virus NS2 protein contributes to virus particle assembly via opposing epistatic interactions with the E1-E2 glycoprotein and NS3-NS4A enzyme complexes." J. Virol. (83):8379-95.
- Lindenbach, B.D., et al. (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.
- Lindenbach, B.D., et al. (2005). "Complete replication of hepatitis C virus in cell culture." Science 309:623-626.
- Lindenbach, B.D., Thiel, H.-J., Rice, C.M. (2007) "Flaviviridae: the viruses and their replication", Fields Virology, 5th Ed.
- Lindenbach BD, Rice CM. (2005) "Unravelling hepatitis C virus replication from genome to function." Nature 436, 933-938.