Increased Expression of LDL Receptor-Related Protein 1 during Human Cytomegalovirus Infection Reduces Virion Cholesterol and Infectivity

Thomas Shenket al. Cell Host Microbe. (2012) 12, 86–96.

Speaker: Yi-Pin Tsai (蔡佾頻)                               Time: 15:00~16:00, April 10, 2013

Commentator: Dr. Kung-Chia Young (楊孔嘉)    Place: Room 601

Abstract

Human cytomegalovirus (HCMV) infects more than 60% of adults. HCMV infection can be life-threatening for the immunocompromised patients and is implicated in cardiovascular diseases. HCMV has been shown to take advantages of several host cell surface proteins for its replication. In the present study, the authors discovered that after HCMV infection, the level of low density lipoprotein related receptor 1 (LRP1), a cell surface protein, is transiently elevated. It has been shown that LRP1 down-regulates intracellular cholesterol and that both HCMV and LRP1 contribute to the development of atherogenic lesions, so the authors focused on the role of LRP1 in HCMV infection. They found that after HCMV infection, the level of LRP1 was increased as early as 6 hours post-infection. At the late phase of infection, LRP1 was cleaved into soluble form resulting in the reduced level of surface LRP1 in infected cells. Treatment of siRNA or antibody specific to LRP1 significantly increased the level of intracellular cholesterol and infectivity of virus. The increased infectivity of virus was resulted from enriched cholesterol content in virions rather than enhanced production of virus particles. Depletion of cholesterol from virus envelope reduced infectivity by inhibiting fusion of virus envelope with cell membrane. In conclusion, the authors found that after HCMV infection, the level of LRP1 on cell membrane is elevated, and LRP1 reduces HCMV infectivity by decreasing the levels of cholesterol in infected cells and virions which will block the fusion of virus envelope and cell membrane.

References:

1.          Signaling through LRP1: Protection fromatherosclerosis and beyond. Biochem  Pharmacol. (2011) 81, 1–5.

2.          Low-density lipoprotein receptorrelatedprotein 1: new functions for an old molecule. Clin. Chem. Lab. Med. (2011) 49, 967–970.