Graduate student

Microbiology and Molecular Genetics

Virology

Harvard Medical School (Boston, MA)

Priscilla L Yang

Characterization of the roles of specific lipid metabolites in viral replication.

Host generated lipid is essential for productive virus replication. However, relatively little is known about the impact of viral infection on cellular lipid metabolism, and the specific lipid metabolites utilized by viruses have not yet been examined. We have applied liquid chromatography-mass spectroscopy (LC-MS) based untargeted metabolite profiling (UMP) to identify lipid metabolites whose steady-state abundance is significantly altered by replication of hepatitis B virus (HBV), a major human pathogen that targets the liver. UMP indicated that although major lipid classes were relatively unaffected by HBV, an ion of 367 m/z was overabundant in HBV+ cells by 18-fold. As shown by ion fragmentation mass spectrometry and co-injection with standard the identity of this ion is 7-dehydrocholesterol (7-DHC), an immediate dehydrogenated precursor to cholesterol. Notably, the accumulation of 7-DHC and its esters was proportional to the amount of HBV replication. This suggests that the accumulation of 7-DHC and its esters has biological significance for HBV replication, and may have implications for the effects of chronic HBV infection on host cholesterol metabolism. This work also suggests that HBV selectively utilizes 7-DHC versus other sterols and prompts experiments investigating the functional significance of this enrichment and the elucidation of the mechanism by which it is achieved. Viruses have historically provided critical tools in the investigation of many fundamental processes in biology. We propose that HBV may provide a novel system for characterizing new aspects of the regulation of cholesterol homeostasis and the structure to biological function relationship of sterols in vivo.