title: Barriers to preclinical investigations of anti-dengue immunity and dengue pathogenesis.
abstract: Dengue virus (DENV) is a human pathogen that causes severe and potentially fatal disease in millions of individuals each year. Immune-mediated pathology is thought to underlie many of the complications of DENV infection in humans, but the notable limitations of the available animal models have impeded our knowledge of the interactions between DENV and the immune system. In this Opinion article, we discuss some of the controversies in the field of dengue research relating to the interaction between DENV and the mammalian host. We highlight key barriers hindering our understanding of the molecular pathogenesis of DENV and offer suggestions for the most effective ways in which the role of the immune system in the protection from, and pathology of, DENV infection can be addressed experimentally.
authors: Program in Emerging Infectious Diseases, Graduate Medical School, Duke-National University of Singapore, 8 College Road, 169857, Singapore.
authors: Ashley L
authors: AL
authors: St John
authors: Soman N
authors: SN
authors: Abraham
authors: Duane J
authors: DJ
authors: Gubler
mesh_terms: D000330:Aedes / Q000502:physiology / Q000821:virology; D000818:Animals; D003715:Dengue / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007303:Insect Vectors / Q000502:physiology / Q000821:virology; D012307:Risk Factors
references: J Infect Dis. 1973 Jul;128(1):23-30
references: 4198025
references: Scand J Immunol. 2008 Jun;67(6):618-25
references: 18433405
references: Aust J Exp Biol Med Sci. 1964 Aug;42:465-82
references: 14202187
references: Virology. 2010 Sep 30;405(2):505-12
references: 20663532
references: Cell Host Microbe. 2010 Nov 18;8(5):410-21
references: 21075352
references: Nat Rev Immunol. 2011 Jul 15;11(8):532-43
references: 21760609
references: Antiviral Res. 2008 Nov;80(2):87-93
references: 18619493
references: Emerg Infect Dis. 2003 Jul;9(7):800-9
references: 12899133
references: J Infect Dis. 2001 Dec 1;184(11):1369-73
references: 11709777
references: Lancet. 2002 Jul 27;360(9329):310-2
references: 12147378
references: Lancet. 1999 Oct 23;354(9188):1431-4
references: 10543670
references: Ann Trop Med Parasitol. 1967 Dec;61(4):500-10
references: 5634140
references: J Virol. 2008 Jan;82(1):335-45
references: 17942531
references: PLoS Negl Trop Dis. 2012;6(4):e1624
references: 22530074
references: Lancet. 2007 Nov 10;370(9599):1644-52
references: 17993365
references: J Gen Virol. 2011 Oct;92(Pt 10):2272-2280
references: 21697346
references: Am J Trop Med Hyg. 1997 May;56(5):566-72
references: 9180609
references: J Exp Med. 2010 Apr 12;207(4):793-806
references: 20308361
references: Am J Trop Med Hyg. 2007 Aug;77(2):297-302
references: 17690402
references: Am J Trop Med Hyg. 1981 Sep;30(5):1100-5
references: 7283007
references: J Surg Res. 1993 Feb;54(2):140-4
references: 8479172
references: Cell Microbiol. 2009 Apr;11(4):604-15
references: 19134117
references: Mol Biol Evol. 2003 Oct;20(10):1650-8
references: 12832629
references: Drug Discov Today Dis Models. 2006;3(1):97-103
references: 18087566
references: Trop Med Health. 2011 Dec;39(4 Suppl):3-11
references: 22500131
references: Am J Trop Med Hyg. 1988 Mar;38(2):411-9
references: 3354774
references: PLoS Pathog. 2008 Feb 8;4(2):e17
references: 18266465
references: J Infect Dis. 2000 Jan;181(1):2-9
references: 10608744
references: Am J Trop Med Hyg. 1993 Mar;48(3):324-31
references: 8470771
references: Elife. 2013 Apr 30;2:e00481
references: 23638300
references: Clin Immunol. 2009 Jun;131(3):404-9
references: 19269255
references: Paediatr Int Child Health. 2012 May;32 Suppl 1:5-9
references: 22668442
references: Arch Virol. 2007;152(3):533-42
references: 17106622
references: Nat New Biol. 1973 May 2;243(122):24-6
references: 17319077
references: Clin Microbiol Rev. 1998 Jul;11(3):480-96
references: 9665979
references: J Virol. 2006 Oct;80(20):10208-17
references: 17005698
references: J Infect Dis. 1997 Aug;176(2):322-30
references: 9237696
references: PLoS Pathog. 2010 Feb 12;6(2):e1000790
references: 20168989
references: J Infect Dis. 2004 Apr 15;189(8):1411-8
references: 15073678
references: Am J Trop Med Hyg. 1983 Jan;32(1):154-6
references: 6824120
references: J Virol. 2012 Apr;86(7):4019-23
references: 22278250
references: Indian Pediatr. 1998 Aug;35(8):727-32
references: 10216566
references: Antiviral Res. 2011 Dec;92(3):453-60
references: 22020302
references: Glob Health Action. 2012;5:
references: 22451836
references: J Infect Dis. 2009 May 15;199(10):1442-8
references: 19392621
references: Am J Trop Med Hyg. 1978 May;27(3):581-9
references: 677371
references: PLoS Negl Trop Dis. 2012;6(3):e1568
references: 22448292
references: J Immunol. 2002 Jun 1;168(11):5959-65
references: 12023403
references: Indian J Med Res. 2006 Jan;123(1):25-30
references: 16567864
references: J Immunol. 2003 Sep 1;171(5):2524-31
references: 12928402
references: Blood. 2010 Mar 4;115(9):1823-34
references: 20042723
references: Nature. 1977 Feb 24;265(5596):739-41
references: 404559
references: J Exp Med. 2003 Apr 7;197(7):823-9
references: 12682107
references: J Immunol. 2002 Dec 15;169(12):6779-86
references: 12471109
references: Proc Natl Acad Sci U S A. 2007 May 29;104(22):9422-7
references: 17517625
references: J Immunol. 1966 Aug;97(2):177-83
references: 5921310
references: J Immunol. 1984 Mar;132(3):1529-32
references: 6607288
references: J Immunol. 2001 Oct 15;167(8):4137-40
references: 11591732
references: Nat Med. 2003 Jul;9(7):921-7
references: 12808447
references: J Infect Dis. 1973 Jul;128(1):7-14
references: 4198027
references: Emerg Infect Dis. 2002 Dec;8(12):1474-9
references: 12498666
references: Nat Med. 2000 Jul;6(7):816-20
references: 10888933
references: Ceylon Med J. 1991 Jun;36(2):63-5
references: 1913986
references: Tissue Antigens. 2004 Oct;64(4):469-72
references: 15361124
references: Vaccine. 2010 Jun 11;28(26):4229-34
references: 20434551
references: Rev Infect Dis. 1989 May-Jun;11 Suppl 4:S830-9
references: 2665015
references: J Virol. 2004 Sep;78(18):9998-10008
references: 15331733
references: Blood. 2011 Nov 17;118(20):5383-93
references: 21908429
references: Am J Trop Med Hyg. 1989 Apr;40(4):444-51
references: 2712199
references: Am J Trop Med Hyg. 2012 Mar;86(3):536-9
references: 22403332
references: Cell Host Microbe. 2010 Feb 18;7(2):128-39
references: 20153282
references: Am J Trop Med Hyg. 1952 Jan;1(1):30-50
references: 14903434
references: Proc Natl Acad Sci U S A. 2011 May 31;108(22):9190-5
references: 21576486
references: Infect Immun. 1981 May;32(2):469-73
references: 7251133