PMID- 30307605
OWN - NLM
STAT- MEDLINE
DCOM- 20191028
LR  - 20200309
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 195
IP  - 1
DP  - 2019 Jan
TI  - Enterovirus infection and type 1 diabetes: unraveling the crime scene.
PG  - 15-24
LID - 10.1111/cei.13223 [doi]
AB  - Enteroviruses (EV) have been historically associated to type 1 diabetes. 
      Definitive proof for their implication in disease development is lacking, but 
      growing evidence suggests that they could be involved in beta cell destruction 
      either directly by killing beta cells or indirectly by creating an exacerbated 
      inflammatory response in the islets, capable of attracting autoreactive T cells 
      to the 'scene of the crime'. Epidemiological and serological studies have been 
      associated with the appearance of islet autoimmunity and EV RNA has been detected 
      in prospective studies. In addition, the EV capsid protein has been detected in 
      the islets of recent-onset type 1 diabetic donors, suggesting the existence of a 
      low-grade EV infection that could become persistent. Increasing evidence in the 
      field shows that a 'viral signature' exists in type 1 diabetes and involves 
      interferon responses that could be sustained during prolonged periods. These 
      include the up-regulation of markers such as protein kinase R (PKR), melanoma 
      differentiation-associated protein 5 (MDA5), retinoic acid inducible gene I 
      (RIG-I), myxovirus resistance protein (MxA) and human leukocyte antigen-I (HLA-I) 
      and the release of chemokines able to attract immune cells to the islets leading 
      to insulitis. In this scenario, the hyperexpression of HLA-I molecules would 
      promote antigen presentation to autoreactive T cells, favoring beta cell 
      recognition and, ultimately, destruction. In this review, an overview is provided 
      of the standing evidence that implicates EVs in beta cell 'murder', the time-line 
      of events is investigated from EV entry in the cell to beta cell death and 
      possible accomplices are highlighted that might be involved in beta cell demise.
CI  - (c) 2018 British Society for Immunology.
FAU - Rodriguez-Calvo, T
AU  - Rodriguez-Calvo T
AD  - Institute for Diabetes Research, Helmholtz Diabetes Center at Helmholtz Zentrum 
      Munchen, Munich, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20181113
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Autoimmunity
MH  - Diabetes Mellitus, Type 1/*immunology
MH  - Enterovirus/*physiology
MH  - Enterovirus Infections/*immunology
MH  - Gene Expression Regulation
MH  - Humans
MH  - Insulin-Secreting Cells/*physiology
MH  - Interferons/genetics/metabolism
MH  - T-Lymphocytes/*immunology
PMC - PMC6300647
OTO - NOTNLM
OT  - beta cell destruction
OT  - interferon response
OT  - type 1 diabetes
OT  - virus infection
EDAT- 2018/10/12 06:00
MHDA- 2019/10/29 06:00
PMCR- 2020/01/01
CRDT- 2018/10/12 06:00
PHST- 2018/07/31 00:00 [received]
PHST- 2018/10/02 00:00 [revised]
PHST- 2018/10/02 00:00 [accepted]
PHST- 2018/10/12 06:00 [pubmed]
PHST- 2019/10/29 06:00 [medline]
PHST- 2018/10/12 06:00 [entrez]
PHST- 2020/01/01 00:00 [pmc-release]
AID - CEI13223 [pii]
AID - 10.1111/cei.13223 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2019 Jan;195(1):15-24. doi: 10.1111/cei.13223. Epub 2018 Nov 
      13.