title: Passive carriage of rabies virus by dendritic cells.
abstract: The rabies virus (RABV) is highly neurotropic and it uses evasive strategies to successfully evade the host immune system. Because rabies is often fatal, understanding the basic processes of the virus-host interactions, particularly in the initial events of infection, is critical for the design of new therapeutic approaches to target RABV. Here, we examined the possible role of dendritic cells (DCs) in the transmission of RABV to neural cells at peripheral site of exposure. Viral replication only occurred at a low level in the DC cell line, JAWS II, after its infection with either pathogenic RABV (CVS strain) or low-pathogenic RABV (ERA strain), and no progeny viruses were produced in the culture supernatants. However, both viral genomic RNAs were retained in the long term after infection and maintained their infectivity. The biggest difference between CVS and ERA was in their ability to induce type I interferons. Although the ERA-infected JAWS II cells exhibited cytopathic effect and were apparently killed by normal spleen cells in vitro, the CVS-infected JAWS II cells showed milder cytopathic effect and less lysis when cocultured with spleen cells. Strongly increased expression of major histocompatibility complex classes I, costimulatory molecules (CD80 and CD86), type I interferons and Toll- like receptor 3, and was observed only in the ERA-inoculated JAWS II cells and not in those inoculated with CVS. During the silencing of the cellular immune response in the DCs, the pathogenic CVS strain cryptically maintained an infectious viral genome and was capable of transmitting infectious RABV to permissive neural cells. These findings demonstrate that DCs may play a role in the passive carriage of RABV during natural rabies infections.
authors.affiliation: Department of Microbiology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu-City, Oita, 879-5593 Japan ; Faculty of Food Science and Nutrition, Beppu University, Beppu, Oita, Japan.
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Senba
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Seiji
authors.initials: S
authors.lastname: Shiota
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Iha
authors.forename: Yukari
authors.initials: Y
authors.lastname: Date
authors.forename: Motoaki
authors.initials: M
authors.lastname: Ohtsubo
authors.forename: Akira
authors.initials: A
authors.lastname: Nishizono
keywords: Dendritic cells; Immune invasion; Rabies virus
references.citation: Infect Immun. 2006 Feb;74(2):984-93
references.pmid: 16428744
references.citation: J Infect Dis. 2004 Feb 15;189(4):658-68
references.pmid: 14767820
references.citation: J Immunol. 2001 Apr 1;166(7):4446-55
references.pmid: 11254700
references.citation: Nat Rev Immunol. 2002 Mar;2(3):151-61
references.pmid: 11913066
references.citation: Acta Neuropathol. 1997 Jul;94(1):73-7
references.pmid: 9224533
references.citation: J Hyg (Lond). 1938 Mar;38(2):180-4
references.pmid: 20475418
references.citation: Nature. 2010 Jun 24;465(7301):1079-83
references.pmid: 20577213
references.citation: Trends Microbiol. 2012 Mar;20(3):139-46
references.pmid: 22325030
references.citation: Adv Virus Res. 2011;79:33-53
references.pmid: 21601041
references.citation: Oral Microbiol Immunol. 2005 Feb;20(1):47-50
references.pmid: 15612946
references.citation: Nature. 1998 Mar 19;392(6673):245-52
references.pmid: 9521319
references.citation: N Engl J Med. 1991 Jan 24;324(4):205-11
references.pmid: 1985241
references.citation: J Virol. 2006 Mar;80(6):2675-83
references.pmid: 16501077
references.citation: Annu Rev Immunol. 1991;9:271-96
references.pmid: 1910679
references.citation: Vaccine. 2008 Jan 17;26(3):419-26
references.pmid: 18082293
references.citation: Lab Invest. 1973 Mar;28(3):361-76
references.pmid: 4266465
references.citation: Adv Virus Res. 2011;79:91-114
references.pmid: 21601044
references.citation: J Immunol. 2000 Jan 1;164(1):64-71
references.pmid: 10604994
references.citation: Microbiol Immunol. 2002;46(6):413-7
references.pmid: 12153119
references.citation: J Virol. 2004 Sep;78(17):9376-88
references.pmid: 15308732
references.citation: J Virol. 1997 Jul;71(7):5603-7
references.pmid: 9188634
references.citation: Cell. 2000 Mar 3;100(5):587-97
references.pmid: 10721995
references.citation: Antiviral Res. 2013 Jul;99(1):61-7
references.pmid: 23369672
references.citation: J Immunol. 1993 Dec 1;151(11):6248-58
references.pmid: 8245464
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19464-9
references.pmid: 18040049
references.citation: Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6328-33
references.pmid: 20304794
references.citation: J Neuroimmunol. 2007 Jul;187(1-2):114-25
references.pmid: 17561271
references.citation: J Virol. 2009 Sep;83(18):9411-22
references.pmid: 19570869
references.citation: J Virol. 2007 May;81(9):4877-80
references.pmid: 17301133
references.citation: J Immunol. 2005 Oct 15;175(8):5260-8
references.pmid: 16210631
references.citation: Curr Infect Dis Rep. 2012 Aug;14(4):408-22
references.pmid: 22699971
references.citation: J Virol. 2003 Oct;77(19):10537-47
references.pmid: 12970438
references.citation: Virus Res. 2012 Apr;165(1):34-45
references.pmid: 22248643
references.citation: Vaccine. 2008 Nov 25;26(50):6441-4
references.pmid: 18804510
references.citation: Endothelium. 2004 May-Aug;11(3-4):169-73
references.pmid: 15370293
references.citation: Virus Res. 2005 Aug;111(2):120-31
references.pmid: 15885837
references.citation: Nat Immunol. 2004 Dec;5(12):1227-34
references.pmid: 15531885
references.citation: Virol J. 2012 Aug 11;9:159
references.pmid: 22882874
references.citation: Science. 2006 Nov 10;314(5801):994-7
references.pmid: 17038590
references.citation: Microbiol Immunol. 2008 Apr;52(4):243-9
references.pmid: 18426399
references.citation: J Virol. 1997 Oct;71(10):7372-80
references.pmid: 9311815
references.citation: J Virol. 2011 Jul;85(13):6657-68
references.pmid: 21525357
references.citation: APMIS. 2003 Jul-Aug;111(7-8):776-88
references.pmid: 12974779
references.citation: J Exp Med. 2002 Feb 18;195(4):507-16
references.pmid: 11854363