In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection

Dengue virus (DENV) infection can lead to a complex spectrum of clinical outcomes, ranging from asymptomatic infection to life-threatening severe dengue. The reasons for thus drastically varying manifestations of the disease remain an enigma. Herein, we reported an original discovery of the synergis...

Descripción completa

Detalles Bibliográficos
Autores principales: Deng, Xiao-Mei, Zhao, Ling-Zhai, Liang, Xue-Ying, Li, Dan, Yu, Lei, Zhang, Fu-Chun, Zhang, Hua, Liu, Zhong-Yu, Xu, Pei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249608/
https://www.ncbi.nlm.nih.gov/pubmed/34220783
http://dx.doi.org/10.3389/fmicb.2021.691008
_version_ 1783716932644503552
author Deng, Xiao-Mei
Zhao, Ling-Zhai
Liang, Xue-Ying
Li, Dan
Yu, Lei
Zhang, Fu-Chun
Zhang, Hua
Liu, Zhong-Yu
Xu, Pei
author_facet Deng, Xiao-Mei
Zhao, Ling-Zhai
Liang, Xue-Ying
Li, Dan
Yu, Lei
Zhang, Fu-Chun
Zhang, Hua
Liu, Zhong-Yu
Xu, Pei
author_sort Deng, Xiao-Mei
collection PubMed
description Dengue virus (DENV) infection can lead to a complex spectrum of clinical outcomes, ranging from asymptomatic infection to life-threatening severe dengue. The reasons for thus drastically varying manifestations of the disease remain an enigma. Herein, we reported an original discovery of the synergistic effect between preexisting Epstein–Barr virus (EBV) infection and DENV superinfection in vitro and of a strong correlation of these two viruses in the clinical samples from dengue patients. We showed that (I) DENV-2 infection of an EBV-positive cell line (EBV + Akata cell) reactivated EBV, and it could be blocked by wortmannin treatment. (II) Examination of human peripheral blood mononuclear cell (PBMC) samples from dengue patients revealed significantly elevated cell-associated EBV DNA copy number at the time of hospitalization vs. at the time of disease recovery in most individuals. (III) EBV infection promoted DENV propagation in both EBV-hosting B cells and indirectly in THP-1 cells, supported by the following evidence: (A) EBV + Akata cells were more permissive to DENV-2 infection compared with Akata cells harboring no EBV virus (EBV- Akata cells). (B) Low-molecular weight fraction secreted from EBV + Akata cells could enhance DENV-2 propagation in monocytic THP-1 cells. (C) While reactivation of EBV in EBV + Akata cells further increased DENV-2 yield from this cell line, pharmacological inhibition of EBV replication by acyclovir had the opposite effect. To our knowledge, this is the first investigation demonstrating a positive correlation between EBV and DENV in vitro and in human biospecimens.
format Online
Article
Text
id pubmed-8249608
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-82496082021-07-03 In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection Deng, Xiao-Mei Zhao, Ling-Zhai Liang, Xue-Ying Li, Dan Yu, Lei Zhang, Fu-Chun Zhang, Hua Liu, Zhong-Yu Xu, Pei Front Microbiol Microbiology Dengue virus (DENV) infection can lead to a complex spectrum of clinical outcomes, ranging from asymptomatic infection to life-threatening severe dengue. The reasons for thus drastically varying manifestations of the disease remain an enigma. Herein, we reported an original discovery of the synergistic effect between preexisting Epstein–Barr virus (EBV) infection and DENV superinfection in vitro and of a strong correlation of these two viruses in the clinical samples from dengue patients. We showed that (I) DENV-2 infection of an EBV-positive cell line (EBV + Akata cell) reactivated EBV, and it could be blocked by wortmannin treatment. (II) Examination of human peripheral blood mononuclear cell (PBMC) samples from dengue patients revealed significantly elevated cell-associated EBV DNA copy number at the time of hospitalization vs. at the time of disease recovery in most individuals. (III) EBV infection promoted DENV propagation in both EBV-hosting B cells and indirectly in THP-1 cells, supported by the following evidence: (A) EBV + Akata cells were more permissive to DENV-2 infection compared with Akata cells harboring no EBV virus (EBV- Akata cells). (B) Low-molecular weight fraction secreted from EBV + Akata cells could enhance DENV-2 propagation in monocytic THP-1 cells. (C) While reactivation of EBV in EBV + Akata cells further increased DENV-2 yield from this cell line, pharmacological inhibition of EBV replication by acyclovir had the opposite effect. To our knowledge, this is the first investigation demonstrating a positive correlation between EBV and DENV in vitro and in human biospecimens. Frontiers Media S.A. 2021-06-18 /pmc/articles/PMC8249608/ /pubmed/34220783 http://dx.doi.org/10.3389/fmicb.2021.691008 Text en Copyright © 2021 Deng, Zhao, Liang, Li, Yu, Zhang, Zhang, Liu and Xu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Deng, Xiao-Mei
Zhao, Ling-Zhai
Liang, Xue-Ying
Li, Dan
Yu, Lei
Zhang, Fu-Chun
Zhang, Hua
Liu, Zhong-Yu
Xu, Pei
In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection
title In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection
title_full In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection
title_fullStr In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection
title_full_unstemmed In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection
title_short In vitro Studies and Clinical Observations Imply a Synergistic Effect Between Epstein-Barr Virus and Dengue Virus Infection
title_sort in vitro studies and clinical observations imply a synergistic effect between epstein-barr virus and dengue virus infection
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249608/
https://www.ncbi.nlm.nih.gov/pubmed/34220783
http://dx.doi.org/10.3389/fmicb.2021.691008
work_keys_str_mv AT dengxiaomei invitrostudiesandclinicalobservationsimplyasynergisticeffectbetweenepsteinbarrvirusanddenguevirusinfection
AT zhaolingzhai invitrostudiesandclinicalobservationsimplyasynergisticeffectbetweenepsteinbarrvirusanddenguevirusinfection
AT liangxueying invitrostudiesandclinicalobservationsimplyasynergisticeffectbetweenepsteinbarrvirusanddenguevirusinfection
AT lidan invitrostudiesandclinicalobservationsimplyasynergisticeffectbetweenepsteinbarrvirusanddenguevirusinfection
AT yulei invitrostudiesandclinicalobservationsimplyasynergisticeffectbetweenepsteinbarrvirusanddenguevirusinfection
AT zhangfuchun invitrostudiesandclinicalobservationsimplyasynergisticeffectbetweenepsteinbarrvirusanddenguevirusinfection
AT zhanghua invitrostudiesandclinicalobservationsimplyasynergisticeffectbetweenepsteinbarrvirusanddenguevirusinfection
AT liuzhongyu invitrostudiesandclinicalobservationsimplyasynergisticeffectbetweenepsteinbarrvirusanddenguevirusinfection
AT xupei invitrostudiesandclinicalobservationsimplyasynergisticeffectbetweenepsteinbarrvirusanddenguevirusinfection