Measles virus infection of the CNS: human disease, animal models, and approaches to therapy.
Viral infections of the central nervous system(CNS) mostly represent clinically important, often life-threatening complications of systemic viral infections. After acute measles, CNS complications may occur early (acute postinfectious measles encephalitis, APME) or after years of viral persistence (subacute sclerosing panencephalitis, SSPE). In spite of a presumably functional cell-mediated immunity and high antiviral antibody titers, an immunological control of the CNS infection is not achieved in patients suffering from SSPE. There is still no specific therapy for acute complications and persistent MV infections of the CNS. Hamsters, rats, and (genetically unmodified and modified) mice have been used as model systems to study mechanisms of MV-induced CNS infections. Functional CD4+ and CD8+ T cells together with IFN-gamma are required to overcome the infection. With the help of recombinant measles viruses and mice expressing endogenous or transgenic receptors, interesting aspects such as receptor-dependent viral spread and viral determinants of virulence have been investigated. However, many questions concerning the lack of efficient immune control in the CNS are still open. Recent research opened new perspectives using specific antivirals such as short interfering RNA (siRNA) or small molecule inhibitors. Inspite of obvious hurdles, these treatments are the most promising approaches to future therapies.
Reuter
Dajana
D
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, Würzburg, Germany.
Schneider-Schaulies
Jürgen
J
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006224:Cricetinae; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008459:Measles virus / Q000276:immunology / Q000302:isolation & purification* / Q000472:pathogenicity; D051379:Mice; D023421:Models, Animal; D034741:RNA, Small Interfering / Q000627:therapeutic use; D051381:Rats; D013344:Subacute Sclerosing Panencephalitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology* / Q000821:virology
D000998:Antiviral Agents; D034741:RNA, Small Interfering; D007371:Interferon-gamma
J Virol. 2001 Aug;75(16):7612-20
11462033
Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4659-63
9114047
J Virol. 1993 Aug;67(8):4760-8
8392613
Virology. 2001 Dec 20;291(2):215-25
11878891
J Virol. 1999 Mar;73(3):1795-801
9971756
J Virol. 2006 Oct;80(19):9361-70
16973542
J Gen Virol. 2007 Nov;88(Pt 11):3112-3120
17947537
Nature. 2000 Aug 24;406(6798):893-7
10972291
J Virol. 2001 Apr;75(7):3059-65
11238832
Epidemiol Infect. 2003 Oct;131(2):887-98
14596530
Drug Saf. 1998 Dec;19(6):435-54
9880088
J Infect Dis. 2005 Nov 15;192(10):1686-93
16235165
J Virol. 2007 Nov;81(21):12066-70
17699577
Clin Diagn Virol. 1995 Aug;4(2):135-47
15566835
J Gen Virol. 2001 Aug;82(Pt 8):1835-1844
11457989
J Neurovirol. 2002 Aug;8(4):335-44
12161818
Neuropediatrics. 2006 Aug;37(4):222-8
17177148
J Neuroimmunol. 1999 May 3;96(2):207-17
10337919
Neuropathol Appl Neurobiol. 1991 Aug;17(4):289-97
1944804
Nature. 1995 Jul 20;376(6537):260-3
7617038
J Virol. 1995 Aug;69(8):5191-4
7609093
J Neurovirol. 1997 Aug;3(4):304-9
9291239
J Gen Virol. 2003 Aug;84(Pt 8):2133-2143
12867645
Antiviral Res. 2009 Mar;81(3):261-6
19133295
J Child Neurol. 2007 Mar;22(3):341-3
17621509
Cell. 1988 Oct 21;55(2):255-65
3167982
J Virol. 2005 Jun;79(12):7768-76
15919929
J Virol. 2009 Jun;83(11):5544-55
19321604
J Virol. 1993 Oct;67(10):6025-32
8371352
J Immunol. 1999 Apr 1;162(7):4024-9
10201924
J Gen Virol. 1997 Jan;78 ( Pt 1):97-106
9010291
Virology. 2006 Mar 30;347(1):234-45
16529787
Cytokine. 2005 Oct 21;32(2):104-10
16226466
Virus Res. 2004 Jan;99(1):51-6
14687946
Neurology. 2004 Feb 10;62(3):457-60
14872030
J Gen Virol. 1998 Nov;79 ( Pt 11):2583-91
9820133
Int J Pharm. 2008 Jun 5;357(1-2):148-53
18329830
J Gen Virol. 2000 Nov;81(Pt 11):2707-2713
11038383
J Virol. 1996 Oct;70(10):6673-81
8794303
J Virol. 1997 Oct;71(10):7969-73
9311889
J Exp Med. 2005 Nov 7;202(9):1185-90
16260490
J Neurol. 2008 Dec;255(12):1861-71
18846316
J Neurovirol. 2001 Feb;7(1):25-34
11519479
Eur J Immunol. 2010 Feb;40(2):388-95
19950186
J Immunol. 1974 Oct;113(4):1205-9
4606230
J Med Virol. 1997 Aug;52(4):362-9
9260681
J Neuropathol Exp Neurol. 1996 Apr;55(4):471-80
8786407
J Pathol. 2006 Jan;208(2):199-214
16362981
J Virol. 1995 Sep;69(9):5469-74
7636992
PLoS One. 2009;4(3):e4948
19319188
J Neurovirol. 2002 Feb;8(1):6-13
11847587
Nat Immunol. 2001 Jan;2(1):64-8
11135580
J Virol. 1988 Apr;62(4):1388-97
3346948
J Virol. 2008 Nov;82(22):11273-82
18768959
Nat Rev Immunol. 2008 Sep;8(9):685-98
19172691
Cochrane Database Syst Rev. 2005 Oct 19;(4):CD001479
16235283
J Virol. 1999 Nov;73(11):9568-75
10516065
J Trop Pediatr. 2002 Apr;48(2):72-7
12022432
Neurol Neurocir Psiquiatr. 1977;18(2-3 Suppl):495-507
616550
Nature. 1981 Apr 16;290(5807):588-9
6783963
J Neuroimmunol. 1984 Dec;7(2-3):77-89
6511890
Neuropathol Appl Neurobiol. 2008 Aug;34(4):424-34
17986184
J Gen Virol. 1997 Jun;78 ( Pt 6):1295-302
9191921
J Med Chem. 2006 Aug 24;49(17):5080-92
16913698
J Virol. 1999 Aug;73(8):6916-22
10400789
Intervirology. 1997;40(2-3):176-84
9450234
Antiviral Res. 2006 Jul;70(3):105-11
16530274
Virology. 2007 Feb 20;358(2):251-7
17070884
J Neurol Sci. 2004 Aug 30;223(2):113-9
15337611
Postgrad Med J. 2002 Feb;78(916):63-70
11807185
J Virol. 2002 Jun;76(11):5720-8
11992000
Bioorg Med Chem Lett. 2007 Sep 15;17(18):5199-203
17643302
J Virol. 2002 May;76(9):4497-506
11932415
J Virol. 2001 May;75(10):4499-505
11312320
J Virol. 1998 Sep;72(9):7420-7
9696838
Virus Res. 1995 Jan;35(1):1-16
7754670
Curr Top Microbiol Immunol. 2009;330:243-69
19203113
J Neurovirol. 2007 Oct;13(5):410-5
17994425
Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16415-20
16260741
J Neuroimmunol. 2005 Dec 30;170(1-2):179-85
16223530
Microbiol Immunol. 2006;50(7):525-34
16858143
J Virol. 2008 May;82(9):4630-7
18287234
J Virol. 2006 Jul;80(13):6420-9
16775330
Brain Res. 2004 Apr 9;1004(1-2):73-82
15033421
Brain Dev. 2010 Jun;32(6):463-6
19481385
Thromb Haemost. 2009 Dec;102(6):1050-6
19967134
J Nutr. 2007 Aug;137(8):1916-22
17634264
Antimicrob Agents Chemother. 2007 Jul;51(7):2293-303
17470652
Int J Epidemiol. 2007 Dec;36(6):1334-48
18037676
J Virol. 2000 Aug;74(16):7478-84
10906201
J Virol. 1994 Mar;68(3):1532-43
8107216
J Gen Virol. 2006 Jul;87(Pt 7):2011-2019
16760404
J Neurovirol. 2000 Apr;6(2):121-6
10822325
J Virol. 2007 Nov;81(21):12091-6
17715217
J Med Chem. 2008 Jul 10;51(13):3731-41
18529043
Virology. 2007 May 25;362(1):235-44
17434199
J Virol. 1992 Sep;66(9):5534-41
1501288
Proc Natl Acad Sci U S A. 1988 Feb;85(4):1252-6
3422488
J Virol. 1993 Jan;67(1):75-81
8093223
J Virol. 2000 Feb;74(3):1373-82
10627548
PLoS Pathog. 2007 Nov;3(11):e178
18020706
J Virol. 2009 Sep;83(18):9423-31
19587038
Antiviral Res. 2004 Jun;62(3):135-7
15130537
J Gen Virol. 2001 Dec;82(Pt 12):2913-2917
11714966
Lancet. 1987 May 9;1(8541):1067-8
2883399
Eur J Neurosci. 1991 Oct;3(1):66-71
12106270
Antimicrob Agents Chemother. 2005 Sep;49(9):3755-61
16127050
Lab Invest. 2002 Apr;82(4):403-9
11950898
Antiviral Res. 2008 Oct;80(1):45-53
18547655
J Gen Virol. 1985 Jul;66 ( Pt 7):1411-21
4020346
Neuropathol Appl Neurobiol. 2003 Jun;29(3):273-9
12787324
Antiviral Res. 2008 Nov;80(2):158-67
18634829
Cell. 1999 Sep 3;98(5):629-40
10490102
J Virol. 2000 Feb;74(4):1908-18
10644364
Cell. 1993 Oct 22;75(2):295-305
8402913
Cytokine. 2006 Jan 7;33(1):17-20
16413199
Arch Neurol. 2002 May;59(5):822-7
12020266
J Immunol. 1980 Jul;125(1):78-85
7381212
J Virol. 2006 Jun;80(12):5951-7
16731933
J Neurovirol. 2008 Nov;14(6):486-91
19016379
J Gen Virol. 1997 Dec;78 ( Pt 12):3227-32
9400973
EMBO J. 1998 Jul 15;17(14):3899-908
9670007
J Clin Invest. 1995 Nov;96(5):2478-81
7593637
J Immunol. 2005 Sep 1;175(5):3252-61
16116216
Virology. 2001 Jan 5;279(1):9-21
11145884
J Virol. 1986 Aug;59(2):472-8
3735490
Immunology. 1994 Oct;83(2):184-9
7835934
Antimicrob Agents Chemother. 1973 Feb;3(2):235-41
4208281
Antimicrob Agents Chemother. 1996 Jan;40(1):241-3
8787915
J Clin Virol. 1999 May;12(3):201-10
10382817
J Immunol. 2003 Sep 15;171(6):3102-9
12960336
Antimicrob Agents Chemother. 2009 Sep;53(9):3860-70
19528268
Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5628-33
15056763
J Clin Invest. 2008 Jul;118(7):2448-58
18568079
FASEB J. 2009 Sep;23(9):3203-12
19447880
Antimicrob Agents Chemother. 1994 Apr;38(4):653-5
8031027
Acta Neuropathol. 1997 Nov;94(5):444-9
9386776
J Virol. 1994 Nov;68(11):6910-7
7933071