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.