PMID- 32153407
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 11
DP  - 2020
TI  - The P2X7 Receptor 489C>T Gain of Function Polymorphism Favors HHV-6A Infection 
      and Associates With Female Idiopathic Infertility.
PG  - 96
LID - 10.3389/fphar.2020.00096 [doi]
LID - 96
AB  - The P2X7 receptor (P2X7R) is an ATP-gated ion channel known for its 
      proinflammatory activity. Despite its participation in host defense against 
      pathogens, the role played in viral infections, notably those caused by herpes 
      viruses, has been seldom studied. Here we investigated the effect of P2X7R 
      expression on human herpes virus 6 A (HHV-6A) infection of P2X7R-expressing 
      HEK293 cells. We show that functional P2X7R increases while its blockade 
      decreases viral load. Interestingly, HHV-6A infection was enhanced in HEK293 
      cells transfected with P2X7R cDNA bearing the gain of function 489C>T SNP 
      (rs208294, replacing a histidine for tyrosine at position 155). The P2X7R 489C>T 
      polymorphism correlated with HHV-6A infection also in a cohort of 50 women 
      affected with idiopathic infertility, a condition previously shown to correlate 
      with HHV-6A infection. None of the infertile women infected by HHV-6A was 
      homozygote for 489CC genotype, while on the contrary HHV-6A infection 
      significantly associated with the presence of the rs208294 allele. Levels of 
      soluble human leukocyte antigen G (sHLA-G), a factor promoting embryo implant, 
      measured in uterine flushings negatively correlated with the 489TT genotype and 
      HHV-6A infection, while proinflammatory cytokines interleukins 1alpha (IL-1alpha), 1beta 
      (IL-1beta), and 8 (IL-8) positively correlated with both the 489T allele presence 
      and viral infection. Taken together these data point to the P2X7R as a new 
      therapeutic target to prevent HHV-6A infection and the associated infertility.
CI  - Copyright (c) 2020 Pegoraro, Bortolotti, Marci, Caselli, Falzoni, De Marchi, Di 
      Virgilio, Rizzo and Adinolfi.
FAU - Pegoraro, Anna
AU  - Pegoraro A
AD  - Department of Morphology, Surgery and Experimental Medicine, University of 
      Ferrara, Ferrara, Italy.
FAU - Bortolotti, Daria
AU  - Bortolotti D
AD  - Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
FAU - Marci, Roberto
AU  - Marci R
AD  - Department of Morphology, Surgery and Experimental Medicine, University of 
      Ferrara, Ferrara, Italy.
AD  - Obstetrics and Gynaecology, School of Medicine, University of Geneve, Geneve, 
      Switzerland.
FAU - Caselli, Elisabetta
AU  - Caselli E
AD  - Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
FAU - Falzoni, Simonetta
AU  - Falzoni S
AD  - Department of Morphology, Surgery and Experimental Medicine, University of 
      Ferrara, Ferrara, Italy.
FAU - De Marchi, Elena
AU  - De Marchi E
AD  - Department of Morphology, Surgery and Experimental Medicine, University of 
      Ferrara, Ferrara, Italy.
FAU - Di Virgilio, Francesco
AU  - Di Virgilio F
AD  - Department of Morphology, Surgery and Experimental Medicine, University of 
      Ferrara, Ferrara, Italy.
FAU - Rizzo, Roberta
AU  - Rizzo R
AD  - Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
FAU - Adinolfi, Elena
AU  - Adinolfi E
AD  - Department of Morphology, Surgery and Experimental Medicine, University of 
      Ferrara, Ferrara, Italy.
LA  - eng
PT  - Journal Article
DEP - 20200221
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC7046806
OTO - NOTNLM
OT  - HHV-6A infection
OT  - HLA-G
OT  - P2X7
OT  - P2X7 489C>T polymorphism
OT  - female infertility
EDAT- 2020/03/11 06:00
MHDA- 2020/03/11 06:01
PMCR- 2020/02/21
CRDT- 2020/03/11 06:00
PHST- 2019/10/30 00:00 [received]
PHST- 2020/01/27 00:00 [accepted]
PHST- 2020/03/11 06:00 [entrez]
PHST- 2020/03/11 06:00 [pubmed]
PHST- 2020/03/11 06:01 [medline]
PHST- 2020/02/21 00:00 [pmc-release]
AID - 10.3389/fphar.2020.00096 [doi]
PST - epublish
SO  - Front Pharmacol. 2020 Feb 21;11:96. doi: 10.3389/fphar.2020.00096. eCollection 
      2020.