PMID- 30574140
OWN - NLM
STAT- MEDLINE
DCOM- 20191002
LR  - 20210129
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 9
DP  - 2018
TI  - Induction of Proinflammatory Multiple Sclerosis-Associated Retrovirus Envelope 
      Protein by Human Herpesvirus-6A and CD46 Receptor Engagement.
PG  - 2803
LID - 10.3389/fimmu.2018.02803 [doi]
LID - 2803
AB  - The aberrant expression of human endogenous retrovirus (HERV) elements of the 
      HERV-W family has been associated with different diseases, including multiple 
      sclerosis (MS). In particular, the expression of the envelope protein (Env) from 
      the multiple sclerosis-associated retrovirus (MSRV), a member of HERV-W family 
      and known for its potent proinflammatory activity, is repeatedly detected in the 
      brain lesions and blood of MS patients. Furthermore, human herpesvirus 6 (HHV-6) 
      infection has long been suspected to play a role in the pathogenesis of MS and 
      neuroinflammation. We show here that both HHV-6A and stimulation of its receptor, 
      transmembrane glycoprotein CD46, induce the expression of MSRV-Env. The 
      engagement of extracellular domains SCR3 and SCR4 of CD46-Cyt1 isoform was 
      required for MSRV-env transactivation, limiting thus the MSRV-Env induction to 
      the CD46 ligands binding these domains, including C3b component of complement, 
      specific monoclonal antibodies, and both infectious and UV-inactivated HHV-6A, 
      but neither HHV-6B nor measles virus vaccine strain. Induction of MSRV-Env 
      required CD46 Cyt-1 singling and was abolished by the inhibitors of protein 
      kinase C. Finally, both membrane-expressed and secreted MSRV-Env trigger TLR4 
      signaling, displaying thus a proinflammatory potential, characteristic for this 
      viral protein. These data expand the specter of HHV-6A effects in the modulation 
      of the immune response and support the hypothesis that cross-talks between 
      exogenous and endogenous viruses may contribute to inflammatory diseases and 
      participate in neuroinflammation. Furthermore, they reveal a new function of 
      CD46, known as an inhibitor of complement activation and receptor for several 
      pathogens, in transactivation of HERV env genes, which may play an important role 
      in the pathogenesis of inflammatory diseases.
FAU - Charvet, Benjamin
AU  - Charvet B
AD  - International Centre for Infectiology Research, INSERM U1111, CNRS UMR5308, Ecole 
      Normale Superieure de Lyon, University of Lyon, Lyon, France.
AD  - GeNeuro Innovation, Lyon, France.
FAU - Reynaud, Josephine M
AU  - Reynaud JM
AD  - International Centre for Infectiology Research, INSERM U1111, CNRS UMR5308, Ecole 
      Normale Superieure de Lyon, University of Lyon, Lyon, France.
FAU - Gourru-Lesimple, Geraldine
AU  - Gourru-Lesimple G
AD  - International Centre for Infectiology Research, INSERM U1111, CNRS UMR5308, Ecole 
      Normale Superieure de Lyon, University of Lyon, Lyon, France.
FAU - Perron, Herve
AU  - Perron H
AD  - GeNeuro Innovation, Lyon, France.
FAU - Marche, Patrice N
AU  - Marche PN
AD  - Institute for Advanced Biosciences, INSERM U1209, CNRS UMR5309, Universite 
      Grenoble-Alpes, IAPC, La Tronche, France.
FAU - Horvat, Branka
AU  - Horvat B
AD  - International Centre for Infectiology Research, INSERM U1111, CNRS UMR5308, Ecole 
      Normale Superieure de Lyon, University of Lyon, Lyon, France.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20181206
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (CD46 protein, human)
RN  - 0 (ERVFRD-1 protein, human)
RN  - 0 (Membrane Cofactor Protein)
RN  - 0 (Pregnancy Proteins)
SB  - IM
MH  - Cell Line, Tumor
MH  - *Endogenous Retroviruses/genetics/immunology/metabolism
MH  - *Herpesvirus 6, Human/immunology/metabolism
MH  - Humans
MH  - Inflammation/genetics/immunology/pathology/virology
MH  - *Membrane Cofactor Protein/immunology/metabolism
MH  - *Multiple Sclerosis/genetics/immunology/metabolism/virology
MH  - *Pregnancy Proteins/biosynthesis/genetics/immunology
MH  - Protein Domains
MH  - *Roseolovirus Infections/genetics/immunology/metabolism
PMC - PMC6291489
OTO - NOTNLM
OT  - CD46
OT  - HHV-6A
OT  - MSRV
OT  - TLR4
OT  - human endogenous retrovirus
OT  - inflammation
OT  - multiple sclerosis
EDAT- 2018/12/24 06:00
MHDA- 2019/10/03 06:00
PMCR- 2018/01/01
CRDT- 2018/12/22 06:00
PHST- 2018/08/02 00:00 [received]
PHST- 2018/11/13 00:00 [accepted]
PHST- 2018/12/22 06:00 [entrez]
PHST- 2018/12/24 06:00 [pubmed]
PHST- 2019/10/03 06:00 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2018.02803 [doi]
PST - epublish
SO  - Front Immunol. 2018 Dec 6;9:2803. doi: 10.3389/fimmu.2018.02803. eCollection 
      2018.