title: Role of chemokines in rabies pathogenesis and protection.
abstract: Chemokines are a family of structurally related proteins that are expressed by almost all types of nucleated cells and mediate leukocyte activation and/or chemotactic activities. The role of chemokines in rabies pathogenesis and protection has only recently been investigated. Expression of chemokines is induced by infection with laboratory-adapted, but not street, rabies viruses (RABVs), and it has been hypothesized that expression of chemokines is one of the mechanisms by which RABV is attenuated. To further define the role of chemokines in rabies pathogenesis and protection, chemokine genes such as MIP-1α, RANTES, IP-10, and macrophage-derived chemokine (MDC) have been cloned into RABV genome. It has been found that recombinant RABVs expressing RANTES or IP-10 induce high and persistent expression of these chemokines, resulting in massive infiltration of inflammatory cells into the central nervous system (CNS) and development of diseases and death in the mouse model. However, recombinant RABVs expressing MIP-1α, MDC, as well as GM-CSF further attenuate RABV by inducing a transient expression of chemokines, infiltration of inflammatory cells, enhancement of blood-brain barrier (BBB) permeability. Yet, these recombinant RABVs show increased adaptive immune responses by recruiting/activating dendritic cells, T and B cells in the periphery as well as in the CNS. Further, direct administration of these recombinant RABVs into the CNS can prevent mice from developing rabies days after infection with street RABV. All these studies together suggest that chemokines are both protective and pathogenic in RABV infections. Those with protective roles could be exploited for development of future RABV vaccines or therapeutic agents.
authors: Department of Pathology, University of Georgia, Athens, Georgia, USA.
authors: Xuefeng
authors: X
authors: Niu
authors: Hualei
authors: H
authors: Wang
authors: Zhen F
authors: ZF
authors: Fu
references: J Immunol. 1994 Feb 1;152(3):1411-8
references: 8301141
references: J Virol. 2008 Oct;82(20):10295-301
references: 18684827
references: J Immunol. 2001 Oct 1;167(7):4091-7
references: 11564831
references: Glia. 2009 Aug 15;57(11):1216-26
references: 19191335
references: J Virol. 2010 Apr;84(8):4002-12
references: 20130065
references: Autoimmunity. 2009 Sep;42(6):484-91
references: 19626487
references: J Virol. 2005 Sep;79(18):11801-12
references: 16140757
references: Curr Top Microbiol Immunol. 2001;253:145-55
references: 11417132
references: J Immunol. 2004 Apr 1;172(7):4018-25
references: 15034013
references: J Exp Med. 2005 Oct 17;202(8):1087-98
references: 16230476
references: J Neuropathol Exp Neurol. 2003 Jun;62(6):593-604
references: 12834104
references: Blood. 1999 Sep 15;94(6):1890-8
references: 10477717
references: Eur J Immunol. 1999 May;29(5):1617-25
references: 10359116
references: J Virol. 1998 May;72(5):3711-9
references: 9557653
references: Proc Natl Acad Sci U S A. 1996 May 28;93(11):5653-8
references: 8643632
references: J Immunol. 2008 Feb 15;180(4):2641-9
references: 18250476
references: PLoS Pathog. 2010 Jul 29;6(7):e1000937
references: 20686655
references: Int Immunol. 1999 Jan;11(1):81-8
references: 10050676
references: J Virol. 2010 Sep;84(18):9642-8
references: 20592092
references: Biochim Biophys Acta. 2011 Feb;1812(2):220-30
references: 20692338
references: J Neurovirol. 2005 Dec;11(6):571-81
references: 16338751
references: Virus Res. 2009 Sep;144(1-2):18-26
references: 19720239
references: J Virol. 2005 Jun;79(11):7113-20
references: 15890951
references: J Exp Med. 1997 May 5;185(9):1595-604
references: 9151897
references: J Virol. 2011 Feb;85(4):1634-44
references: 21106736
references: Nature. 2009 Jan 8;457(7226):191-5
references: 19011611
references: J Virol. 2003 Aug;77(16):8729-35
references: 12885892
references: J Exp Med. 1991 Dec 1;174(6):1425-9
references: 1683893
references: J Leukoc Biol. 1999 Aug;66(2):224-30
references: 10449158
references: J Virol. 2005 Oct;79(19):12554-65
references: 16160183
references: J Virol. 2009 Sep;83(17):8604-15
references: 19515766
references: J Virol. 2004 Sep;78(17):9376-88
references: 15308732
references: Immunity. 2000 Feb;12(2):121-7
references: 10714678
references: Int J Infect Dis. 2000;4(4):222-8
references: 11231187
references: Curr Top Microbiol Immunol. 2001;253:219-45
references: 11417137
references: Curr Top Microbiol Immunol. 1994;187:1-26
references: 7859487
references: J Virol. 2007 Feb;81(3):1110-8
references: 17108029
references: Vaccine. 1997 Spring;15 Suppl:S20-4
references: 9218287
references: Cell Immunol. 2003 Aug;224(2):106-13
references: 14609576
references: J Immunol. 2006 Jun 15;176(12):7666-75
references: 16751414
references: J Immunol. 2006 Apr 1;176(7):4235-43
references: 16547260
references: Am J Pathol. 2010 Nov;177(5):2433-45
references: 20864677
references: J Immunol. 2001 Nov 1;167(9):4791-5
references: 11673480
references: Immunol Cell Biol. 2009 Jan;87(1):91-9
references: 18794906
references: J Neurovirol. 1999 Dec;5(6):623-34
references: 10602403
references: J Neurovirol. 2007 Apr;13(2):107-17
references: 17505979
references: J Virol. 2010 Aug;84(15):7703-12
references: 20484496
references: Int J Biochem Cell Biol. 2004 Oct;36(10):1882-6
references: 15203102
references: J Neurovirol. 2008 May;14(3):218-28
references: 18569456
references: J Exp Med. 2006 Jan 23;203(1):35-40
references: 16418398
references: Brain Behav Immun. 1995 Dec;9(4):331-44
references: 8903850
references: Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15511-6
references: 18829442
references: Vet Clin North Am Small Anim Pract. 2008 Jul;38(4):851-61, ix
references: 18501283
references: Gene Ther. 2010 Jan;17(1):72-82
references: 19847203
references: J Exp Med. 2001 Sep 17;194(6):847-53
references: 11560999
references: Eur J Immunol. 2004 Apr;34(4):1011-20
references: 15048711
references: Adv Immunol. 2001;78:57-110
references: 11432208
references: Science. 1999 Dec 10;286(5447):2098-102
references: 10617422
references: J Neurovirol. 2001 Dec;7(6):518-27
references: 11704884
references: J Exp Med. 1997 Mar 3;185(5):801-3
references: 9120385
references: Nat Immunol. 2001 Feb;2(2):123-8
references: 11175804
references: Trends Pharmacol Sci. 2006 Jan;27(1):48-55
references: 16310865
references: J Virol. 2007 Aug;81(15):7993-8
references: 17507463
references: Bioessays. 1999 Jan;21(1):17-28
references: 10070251
references: J Virol. 2009 Nov;83(22):11808-18
references: 19740983
references: J Virol. 1993 Nov;67(11):6674-81
references: 8411369
references: J Virol. 2005 Oct;79(20):12893-904
references: 16188991
references: Annu Rev Immunol. 2000;18:217-42
references: 10837058
references: J Exp Med. 1998 Aug 3;188(3):451-63
references: 9687523
references: Growth Factors. 2004 Dec;22(4):225-31
references: 15621725
references: J Immunol. 2003 Sep 15;171(6):3102-9
references: 12960336
references: Cell Immunol. 2002 Jul-Aug;218(1-2):74-86
references: 12470615
references: J Exp Med. 1967 Mar 1;125(3):447-56
references: 6016898
references: J Immunol. 2009 Jan 15;182(2):1079-87
references: 19124751
references: J Neuroimmune Pharmacol. 2008 Mar;3(1):5-11
references: 18066668
references: J Virol. 2007 Apr;81(8):3704-13
references: 17267483
references: Blood. 2008 Jan 15;111(2):485-91
references: 18182579
references: PLoS Negl Trop Dis. 2009 Oct 06;3(10):e535
references: 19806203
references: Arch Virol. 1977;54(4):279-97
references: 907476
references: Viral Immunol. 2008 Dec;21(4):425-33
references: 19115931