title: The purinergic receptor P2X7 role in control of Dengue virus-2 infection and cytokine/chemokine production in infected human monocytes.
abstract: Purinergic signaling has a crucial role in intracellular pathogen elimination. The P2X7 purinergic receptor (P2X7R), once activated by ATP, leads to pro-inflammatory responses including reactive oxygen species production. ATP can be released by injured cells, as endogenous danger signals. Dengue fever may evolve to a severe disease, leading to hypovolemic shock and coagulation dysfunctions as a result of a cytokine storm. Our aim was to evaluate the role of P2X7R activation during Dengue virus (DENV) infection. Extracellular ATP inhibited viral load in pretreated monocytes, as measured by NS1 secretion and by decrease in DENV(+) P2X7(+) cell frequencies, suggesting that P2X7R is involved in the antiviral response. Nitric oxide (NO) has anti-DENV properties and is decreased after DENV infection. NO production after ATP stimulation is abrogated by KN62 treatment, a specific P2X7R inhibitor, indicating that P2X7R likely is acting in the virus containment process. Additionally, TNF, CXCL8, CCL2 and CXCL10 factors that are associated with dengue severity were modulated by the P2X7R activation. We conclude that P2X7R is directly involved in the modulation of the antiviral and inflammatory process that occurs during DENV infection in vitro, and may have an important role in patient recovery in a first moment.
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil. Electronic address: gladys.correa@ioc.fiocruz.br.
authors.forename: Gladys
authors.initials: G
authors.lastname: Corrêa
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil.
authors.forename: Carolina
authors.initials: C
authors.lastname: de A Lindenberg
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil.
authors.forename: Caroline
authors.initials: C
authors.lastname: Fernandes-Santos
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Gandini
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Petitinga Paiva
authors.affiliation: Laboratório de Imunofisiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: Robson
authors.initials: R
authors.lastname: Coutinho-Silva
authors.affiliation: Laboratório de Imunologia Viral, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Brazil.
authors.forename: Claire
authors.initials: C
authors.lastname: F Kubelka
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D009569:Nitric Oxide / Q000378:metabolism; D058486:Receptors, Purinergic P2X7 / Q000235:genetics / Q000378:metabolism*; D019562:Viral Load
chemical_list: D018925:Chemokines; D016207:Cytokines; D058486:Receptors, Purinergic P2X7; D009569:Nitric Oxide; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate
keywords: Dengue; Monocytes; P2X7 receptor; Purinergic signaling