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/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence: by the demonstration that endocytosis of these virus c...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 96; no. 22; pp. 12766 - 12771
Main Authors Agnello, Vincent, Ábel, György, Elfahal, Mutasim, Knight, Glenn B., Zhang, Qing-Xiu
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 26.10.1999
National Acad Sciences
National Academy of Sciences
The National Academy of Sciences
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Abstract Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence: by the demonstration that endocytosis of these virus correlated with LDL receptor activity, by complete inhibition of detectable endocytosis by anti-LDL receptor antibody, by inhibition with anti-apolipoprotein E and -apolipoprotein B antibodies, by chemical methods abrogating lipoprotein/LDL receptor interactions, and by inhibition with the endocytosis inhibitor phenylarsine oxide. Confirmatory evidence was provided by the lack of detectable LDL receptor on cells known to be resistant to BVDV infection. Endocytosis via the LDL receptor was shown to be mediated by complexing of the virus to very low density lipoprotein or LDL but not high density lipoprotein. Studies using LDL receptor-deficient cells or a cytolytic BVDV 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 indicated that this mechanism may not be exclusive to Flaviviridae but may be used by viruses that associated with lipoprotein in the blood. These findings provide evidence that the family of LDL receptors may serve as viral receptors.
AbstractList Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence: by the demonstration that endocytosis of these virus correlated with LDL receptor activity, by complete inhibition of detectable endocytosis by anti-LDL receptor antibody, by inhibition with anti-apolipoprotein E and -apolipoprotein B antibodies, by chemical methods abrogating lipoprotein/LDL receptor interactions, and by inhibition with the endocytosis inhibitor phenylarsine oxide. Confirmatory evidence was provided by the lack of detectable LDL receptor on cells known to be resistant to BVDV infection. Endocytosis via the LDL receptor was shown to be mediated by complexing of the virus to very low density lipoprotein or LDL but not high density lipoprotein. Studies using LDL receptor-deficient cells or a cytolytic BVDV 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 indicated that this mechanism may not be exclusive to Flaviviridae but may be used by viruses that associate with lipoprotein in the blood. These findings provide evidence that the family of LDL receptors may serve as viral receptors.
Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence: by the demonstration that endocytosis of these virus correlated with LDL receptor activity, by complete inhibition of detectable endocytosis by anti-LDL receptor antibody, by inhibition with anti-apolipoprotein E and -apolipoprotein B antibodies, by chemical methods abrogating lipoprotein/LDL receptor interactions, and by inhibition with the endocytosis inhibitor phenylarsine oxide. Confirmatory evidence was provided by the lack of detectable LDL receptor on cells known to be resistant to BVDV infection. Endocytosis via the LDL receptor was shown to be mediated by complexing of the virus to very low density lipoprotein or LDL but not high density lipoprotein. Studies using LDL receptor-deficient cells or a cytolytic BVDV 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 indicated that this mechanism may not be exclusive to Flaviviridae but may be used by viruses that associated with lipoprotein in the blood. These findings provide evidence that the family of LDL receptors may serve as viral receptors.
Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by low density lipoprotein (LDL) receptors on cultured cells by several lines of evidence.
Author Elfahal, Mutasim
Agnello, Vincent
Zhang, Qing-Xiu
Ábel, György
Knight, Glenn B.
AuthorAffiliation Lahey Clinic Medical Center, Department of Laboratory Medicine, Burlington, MA 01805; and † Edith Nourse Rogers Memorial Veterans Affairs Hospital, Bedford, MA 01730
AuthorAffiliation_xml – name: Lahey Clinic Medical Center, Department of Laboratory Medicine, Burlington, MA 01805; and † Edith Nourse Rogers Memorial Veterans Affairs Hospital, Bedford, MA 01730
Author_xml – sequence: 1
  givenname: Vincent
  surname: Agnello
  fullname: Agnello, Vincent
– sequence: 2
  givenname: György
  surname: Ábel
  fullname: Ábel, György
– sequence: 3
  givenname: Mutasim
  surname: Elfahal
  fullname: Elfahal, Mutasim
– sequence: 4
  givenname: Glenn B.
  surname: Knight
  fullname: Knight, Glenn B.
– sequence: 5
  givenname: Qing-Xiu
  surname: Zhang
  fullname: Zhang, Qing-Xiu
BackLink https://www.ncbi.nlm.nih.gov/pubmed/10535997$$D View this record in MEDLINE/PubMed
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To whom reprint requests should be addressed at: Department of Laboratory Medicine, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA 01805. E-mail: Vincent.Agnello@Lahey.org.
Edited by Robert J. Lefkowitz, Duke University Medical Center, Durham, NC, and approved August 24, 1999
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Snippet Endocytosis of the Flaviviridae viruses, hepatitis C virus, GB virus C/hepatitis G virus, and bovine viral diarrheal virus (BVDV) was shown to be mediated by...
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SubjectTerms Animals
Antibodies
B lymphocytes
Biological Sciences
Bovine viral diarrhea virus
Cell Line
Cell lines
Cells
Cultured cells
Endocytosis
Flaviviridae
Flaviviridae - physiology
Hepacivirus - physiology
Hepatitis
Hepatitis C
Hepatitis C virus
Hepatitis G virus
Humans
Infections
LDL receptors
Lipids
Lipoproteins
low density lipoprotein
Proteins
Receptors
Receptors, LDL - physiology
Receptors, Virus - physiology
Virus Replication
Viruses
Title Hepatitis C Virus and other Flaviviridae Viruses Enter Cells via Low Density Lipoprotein Receptor
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Volume 96
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