PMID- 25473057
OWN - NLM
STAT- MEDLINE
DCOM- 20150408
LR  - 20181113
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 89
IP  - 4
DP  - 2015 Feb
TI  - The inability of wild-type rabies virus to activate dendritic cells is dependent 
      on the glycoprotein and correlates with its low level of the de novo-synthesized 
      leader RNA.
PG  - 2157-69
LID - 10.1128/JVI.02092-14 [doi]
AB  - Dendritic cells (DCs) are the most efficient antigen-presenting cells, playing a 
      key role in the adaptive immune responses to viral infections. Our studies 
      demonstrate that wild-type (wt) rabies virus (RABV) does not activate DCs. 
      Adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate 
      virus neutralizing antibodies (VNA), or protect recipients against challenge. 
      However, adoptive transfer of DCs primed with laboratory-attenuated RABV resulted 
      in DC activation, production of VNA, and protection against challenge. In vitro 
      studies with recombinant RABV (laboratory-attenuated RABV expressing the 
      glycoprotein or the phosphoprotein from wt RABV) demonstrate that DC activation 
      is dependent on the glycoprotein and involves the IPS-1 pathway. Furthermore, 
      binding to and entry into DCs by wt RABV is severely blocked, and the copy number 
      of de novo-synthesized leader RNA was two logs lower in DCs infected with the wt 
      than in DCs treated with laboratory-attenuated RABV. However, transient 
      transfection of DCs with synthesized leader RNA from either wt or attenuated RABV 
      is capable of activating DCs in a dose-dependent manner. Thus, the inability of 
      wt RABV to activate DCs correlates with its low level of the de novo-synthesized 
      leader RNA. IMPORTANCE: Rabies remains a public health threat, with more than 
      55,000 fatalities each year around the world. Since DCs play a key role in the 
      adaptive immune responses to viral infections, we investigated the ability of 
      rabies virus (RABV) to activate DCs. It was found that the adoptive transfer of 
      DCs primed with wt RABV did not activate DCs, stimulate VNA, or protect mice 
      against lethal challenge. However, laboratory-attenuated RABV mediates the 
      activation of DCs via the IPS-1 pathway and is glycoprotein dependent. We further 
      show that wt RABV evades DC-mediated immune activation by inefficient 
      binding/entry into DCs and as a result of a reduced level of de novo-synthesized 
      leader RNA. These findings may have important implications in the development of 
      efficient rabies vaccines.
CI  - Copyright (c) 2015, American Society for Microbiology. All Rights Reserved.
FAU - Yang, Yang
AU  - Yang Y
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan, China Department of Pathology, 
      College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
FAU - Huang, Ying
AU  - Huang Y
AD  - Department of Pathology, College of Veterinary Medicine, University of Georgia, 
      Athens, Georgia, USA.
FAU - Gnanadurai, Clement W
AU  - Gnanadurai CW
AD  - Department of Pathology, College of Veterinary Medicine, University of Georgia, 
      Athens, Georgia, USA.
FAU - Cao, Shengbo
AU  - Cao S
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan, China.
FAU - Liu, Xueqin
AU  - Liu X
AD  - Department of Pathology, College of Veterinary Medicine, University of Georgia, 
      Athens, Georgia, USA.
FAU - Cui, Min
AU  - Cui M
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan, China cuimin@mail.hzau.edu.cn 
      zhenfu@uga.edu.
FAU - Fu, Zhen F
AU  - Fu ZF
AD  - State Key Laboratory of Agricultural Microbiology, College of Veterinary 
      Medicine, Huazhong Agricultural University, Wuhan, China Department of Pathology, 
      College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA 
      cuimin@mail.hzau.edu.cn zhenfu@uga.edu.
LA  - eng
GR  - R01 AI051560/AI/NIAID NIH HHS/United States
GR  - R01 AI093369/AI/NIAID NIH HHS/United States
GR  - AI-051560/AI/NIAID NIH HHS/United States
GR  - AI-093369/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141203
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Glycoproteins)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Animals
MH  - Cells, Cultured
MH  - Dendritic Cells/*immunology/*virology
MH  - Glycoproteins/*immunology
MH  - Mice, Inbred BALB C
MH  - RNA, Viral/genetics
MH  - Rabies virus/*immunology
PMC - PMC4338874
EDAT- 2014/12/05 06:00
MHDA- 2015/04/09 06:00
PMCR- 2015/08/15
CRDT- 2014/12/05 06:00
PHST- 2014/12/05 06:00 [entrez]
PHST- 2014/12/05 06:00 [pubmed]
PHST- 2015/04/09 06:00 [medline]
PHST- 2015/08/15 00:00 [pmc-release]
AID - JVI.02092-14 [pii]
AID - 02092-14 [pii]
AID - 10.1128/JVI.02092-14 [doi]
PST - ppublish
SO  - J Virol. 2015 Feb;89(4):2157-69. doi: 10.1128/JVI.02092-14. Epub 2014 Dec 3.