Hepatitis C virus and other Flaviviridae viruses enter cells via low density lipoprotein receptor

Endocytosis of the Flaviviridae viruses, hepatitis C virus. GB virus C/hepa titis C virus, and bovine viral diarrheal virus (BVDV) was shown to be medi ated by low density lipoprotein (LDL) receptors on cultured cells by severa l lines of evidence: by the demonstration that endocytosis of these virus c orrelated with LDL receptor activity, by complete inhibition of detectable endocytosis by anti-LDL receptor antibody, by inhibition with anti-apolipop rotein E and -apolipoprotein B antibodies, by chemical methods abrogating l ipoprotein/LDL receptor interactions, and by inhibition with the endocytosi s inhibitor phenylarsine oxide. Confirmatory evidence was provided by the l ack of detectable LDL receptor on cells known to be resistant to BVDV infec tion. Endocytosis via the LDL receptor was shown to be mediated by complexi ng of the virus to very low density lipoprotein or LDL but not high density lipoprotein. Studies using LDL receptor-deficient cells or a cytolytic BVD V system indicated that the LDL receptor may be the main but not exclusive means of cell entry of these viruses. Studies on other types of viruses ind icated that this mechanism may not be exclusive to Flaviviridae but may be used by viruses that associate with lipoprotein in the blood. These finding s provide evidence that the family of LDL receptors may serve as viral rece ptors.