Cell Host Microbe 12, 86–96 (2012)

As with all viral infections, infection by the enveloped human cytomegalovirus (HCMV) causes changes in expression in numerous host cell genes, presumably to the benefit of the virus. To characterize the changes that occur in host cell-surface proteins, Gudleski-O'Regan et al. evaluated the proteomes before and after HCMV infection by MS after treatment of intact cells with a cell-impermeable amine-reactive probe. The authors detected 114 proteins differentially expressed on the cell surface after HCMV infection. They focused on LRP1, an LDL receptor–related protein involved in cholesterol uptake, which was transiently increased at 24 h after infection. Both knockdown of LRP1 and HCMV infection are known to lead to increased intracellular cholesterol in fibroblasts; the authors verify these relationships and also find that LRP1 knockdown increases HCMV infectivity and increases cholesterol in released virions. Blocking cholesterol biosynthesis or depleting cholesterol from cells decreased infectivity, verifying the connection between infectivity and increased cholesterol content due to LRP1-mediated uptake. Finally, the authors showed that envelope cholesterol is critical for HCMV fusion with the host cell. These results suggest that increased cellular and virion cholesterol content leads to more efficient fusion of the virion envelope with the plasma membrane and therefore increased virion infectivity.