title: Human apolipoprotein A-I is associated with dengue virus and enhances virus infection through SR-BI.
abstract: Diseases caused by dengue virus (DV) infection vary in severity, with symptoms ranging from mild fever to life threatening dengue hemorrhage fever (DHF) and dengue shock syndrome (DSS). Clinical studies have shown that significant decrease in the level of lipoproteins is correlated with severe illness in DHF/DSS patients. Available evidence also indicates that lipoproteins including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) are able to facilitate cell entry of HCV or other flaviviruses via corresponding lipoprotein receptors. In this study, we found that pre-incubation of DV with human serum leads to an enhanced DV infectivity in various types of cells. Such enhancement could be due to interactions between serum components and DV particles. Through co-immunoprecipitation we revealed that apolipoprotein A-I (ApoA-I), the major protein component in HDL, is associated with DV particles and is able to promote DV infection. Based on that observation, we further found that siRNA knockdown of the scavenger receptor class B type I (SR-BI), the cell receptor of ApoA-I, abolished the activity of ApoA-I in enhancement of DV infection. This suggests that ApoA-I bridges DV particles and cell receptor SR-BI and facilitates entry of DV into cells. FACS analysis of cell surface dengue antigen after virus absorption further confirmed that ApoA-I enhances DV infection via promoting initial attachment of the virus to cells. These findings illustrate a novel entry route of DV into cells, which may provide insights into the functional importance of lipoproteins in dengue pathogenesis.
authors.affiliation: Department of Microbiology, University of Hawaii at Manoa, Honolulu, Hawaii, United States of America.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Li
authors.forename: Cherie
authors.initials: C
authors.lastname: Kakinami
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Baojun
authors.initials: B
authors.lastname: Yang
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D015153:Blotting, Western; D018955:CD36 Antigens / Q000378:metabolism*; D002460:Cell Line; D003715:Dengue / Q000378:metabolism*; D003716:Dengue Virus / Q000472:pathogenicity*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D056945:Hep G2 Cells; D006801:Humans; D047468:Immunoprecipitation; D020298:U937 Cells; D014461:Ultracentrifugation; D014709:Vero Cells
chemical_list: D016632:Apolipoprotein A-I; D018955:CD36 Antigens
references.citation: Curr Opin Lipidol. 2010 Jun;21(3):229-38
references.pmid: 20480549
references.citation: Cell Microbiol. 2007 Oct;9(10):2445-56
references.pmid: 17517063
references.citation: Curr Opin Lipidol. 2003 Apr;14(2):151-7
references.pmid: 12642783
references.citation: Subcell Biochem. 2010;51:183-227
references.pmid: 20213545
references.citation: Int J Biochem Cell Biol. 2004 Jan;36(1):39-77
references.pmid: 14592533
references.citation: J Virol. 2007 May;81(9):4881-5
references.pmid: 17301152
references.citation: J Biol Chem. 1986 Jul 25;261(21):9644-51
references.pmid: 3525531
references.citation: Arterioscler Thromb Vasc Biol. 2006 Aug;26(8):1687-8
references.pmid: 16857958
references.citation: J Biol Chem. 2005 Mar 4;280(9):7793-9
references.pmid: 15632171
references.citation: J Biol Chem. 2006 Apr 21;281(16):11193-204
references.pmid: 16488891
references.citation: Arch Virol. 1999;144(5):989-95
references.pmid: 10416380
references.citation: Antiviral Res. 1999 Jul;42(3):211-8
references.pmid: 10443533
references.citation: Amyloid. 2012 Mar;19(1):5-14
references.pmid: 22320226
references.citation: FASEB J. 2006 Apr;20(6):735-7
references.pmid: 16476701
references.citation: PLoS Pathog. 2009 Feb;5(2):e1000310
references.pmid: 19229312
references.citation: Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12766-71
references.pmid: 10535997
references.citation: Nat Rev Microbiol. 2010 Dec;8(12 Suppl):S7-16
references.pmid: 21079655
references.citation: Arch Virol. 1989;104(1-2):129-43
references.pmid: 2564270
references.citation: J Virol. 2002 Jul;76(14):6919-28
references.pmid: 12072493
references.citation: J Lipid Res. 2005 Sep;46(9):1877-87
references.pmid: 15995179
references.citation: Pediatr Res. 1997 Nov;42(5):651-5
references.pmid: 9357939
references.citation: Hepatology. 2012 Aug;56(2):484-91
references.pmid: 22334503
references.citation: Am J Trop Med Hyg. 2007 Aug;77(2):283-90
references.pmid: 17690400
references.citation: Virology. 2010 Oct 10;406(1):149-61
references.pmid: 20674955
references.citation: Clin Microbiol Rev. 1998 Jul;11(3):480-96
references.pmid: 9665979
references.citation: Annu Rev Biochem. 1999;68:523-58
references.pmid: 10872459
references.citation: Clin Infect Dis. 2002 Apr 15;34(8):1150-3
references.pmid: 11915007
references.citation: J Lipid Res. 2000 Jun;41(6):853-72
references.pmid: 10828078
references.citation: J Gen Virol. 2006 Sep;87(Pt 9):2577-2581
references.pmid: 16894196
references.citation: J Clin Microbiol. 2002 Dec;40(12):4472-8
references.pmid: 12454138
references.citation: Annu Rev Nutr. 2012 Aug 21;32:161-82
references.pmid: 22540255
references.citation: Virology. 2012 Jan 20;422(2):326-37
references.pmid: 22129847
references.citation: J Med Virol. 2000 Nov;62(3):364-76
references.pmid: 11055247
references.citation: Vaccine. 2011 Sep 23;29(42):7276-84
references.pmid: 21781998
references.citation: Trop Med Health. 2011 Dec;39(4 Suppl):37-43
references.pmid: 22500135
references.citation: J Proteome Res. 2009 Dec;8(12):5431-41
references.pmid: 19845402
references.citation: Autoimmun Rev. 2002 Feb;1(1-2):111-7
references.pmid: 12849067
references.citation: J Virol. 2006 Mar;80(5):2418-28
references.pmid: 16474148