The P2X7 Receptor 489C>T Gain of Function Polymorphism Favors HHV-6A Infection and Associates With Female Idiopathic Infertility

Frontiers in Pharmacology
Anna PegoraroElena Adinolfi

Abstract

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 proinflam...Continue Reading

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Citations

Sep 7, 2020·Journal of Cancer Research and Clinical Oncology·Qianqian LiRonglan Zhao
Jan 15, 2021·Microbiology and Molecular Biology Reviews : MMBR·Alexandra Y SoareTalia H Swartz
Jan 23, 2021·Cells·Anna PegoraroElena Adinolfi
Apr 13, 2021·Frontiers in Immunology·Anthony L KomaroffJeffrey L Ecker
Dec 29, 2020·Biochemical Pharmacology·Pablo Pelegrin
Jun 18, 2021·Journal of Medical Virology·Daria BortolottiPantaleo Greco
Oct 2, 2021·Journal of Cellular Physiology·Lucas Sagrillo-FagundesMárcia R Wink

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Methods Mentioned

BETA
PCR
FACS
biopsy
electrophoresis
ELISA
Fluorescence
Infection
biopsies

Software Mentioned

FlowJo LLC
GraphPad Prism

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