In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus

Human adenovirus (HAdV) infection has an important clinical impact in the immunosuppressed population and is associated with high morbidity and mortality rates. The lack of a specific, safe and effective antiviral treatment against HAdV makes necessary the search for new therapeutic options. The aim...

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Autores: Aguilar Guisado, Manuela, Marrugal-Lorenzo, José Antonio, Berastegui-Cabrera, Judith, Merino Díaz, Laura, Pachón, Jerónimo, Sánchez-Céspedes, Javier
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/231344
Acceso en línea:http://hdl.handle.net/10261/231344
Access Level:acceso abierto
Palabra clave:Ganciclovir
Cidofovir
Cytomegalovirus
Adenovirus
Co-infection
HSCT
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spelling In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirusAguilar Guisado, ManuelaMarrugal-Lorenzo, José AntonioBerastegui-Cabrera, JudithMerino Díaz, LauraPachón, JerónimoSánchez-Céspedes, JavierGanciclovirCidofovirCytomegalovirusAdenovirusCo-infectionHSCTHuman adenovirus (HAdV) infection has an important clinical impact in the immunosuppressed population and is associated with high morbidity and mortality rates. The lack of a specific, safe and effective antiviral treatment against HAdV makes necessary the search for new therapeutic options. The aim of this study was to evaluate the in vitro activity of ganciclovir (GCV) against HAdV in co-infection by human cytomegalovirus (HCMV) and HAdV in cellular cultures. Quantitative real-time polymerase chain reaction (qPCR) was used to measure HAdV and HCMV DNA replication efficiency in monocultures and in co-infection situations in the presence of both cidofovir (CDV) and GCV. The effects of GCV and CDV were also evaluated in a burst assay (used to measure the production of virus particles) for both viruses, alone and in combination. GCV decreased by 1-log the HAdV DNA replication efficiency in co-infection with HCMV compared with its activity in HAdV monoculture. The burst assay showed that the reductions in virus yield in the presence of GCV were higher for HCMV and co-infection than for HAdV in monoculture (145.2±35.5- vs. 116.4±27.3- vs. 23.0±10.0-fold, respectively, P<0.05). The improved anti-HAdV activity of GCV during co-infection may be because of the more efficient phosphorylation of GCV by the HCMV protein kinase, UL97. Patients treated with GCV as pre-emptive therapy for HCMV infection may be considered as low-risk for developing HAdV infections; however, further evaluations are required to confirm these results.Supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009) - co‐financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014‐2020, the Carlos III Health Institute (PI15/00489; DTS17/00130; PI18/01191) and the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT) grants.Peer reviewedElsevierInstituto de Salud Carlos IIIMinisterio de Economía y Competitividad (España)Red Española de Investigación en Patología InfecciosaEuropean CommissionSpanish Adenovirus NetworkConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2021202120202021info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttp://hdl.handle.net/10261/231344reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2015-68990-REDThttp://doi.org/10.1016/j.ijantimicag.2020.106046Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2313442026-05-22T06:33:51Z
dc.title.none.fl_str_mv In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus
title In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus
spellingShingle In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus
Aguilar Guisado, Manuela
Ganciclovir
Cidofovir
Cytomegalovirus
Adenovirus
Co-infection
HSCT
title_short In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus
title_full In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus
title_fullStr In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus
title_full_unstemmed In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus
title_sort In vitro co-infection by cytomegalovirus improves the antiviral activity of ganciclovir against human adenovirus
dc.creator.none.fl_str_mv Aguilar Guisado, Manuela
Marrugal-Lorenzo, José Antonio
Berastegui-Cabrera, Judith
Merino Díaz, Laura
Pachón, Jerónimo
Sánchez-Céspedes, Javier
author Aguilar Guisado, Manuela
author_facet Aguilar Guisado, Manuela
Marrugal-Lorenzo, José Antonio
Berastegui-Cabrera, Judith
Merino Díaz, Laura
Pachón, Jerónimo
Sánchez-Céspedes, Javier
author_role author
author2 Marrugal-Lorenzo, José Antonio
Berastegui-Cabrera, Judith
Merino Díaz, Laura
Pachón, Jerónimo
Sánchez-Céspedes, Javier
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Salud Carlos III
Ministerio de Economía y Competitividad (España)
Red Española de Investigación en Patología Infecciosa
European Commission
Spanish Adenovirus Network
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Ganciclovir
Cidofovir
Cytomegalovirus
Adenovirus
Co-infection
HSCT
topic Ganciclovir
Cidofovir
Cytomegalovirus
Adenovirus
Co-infection
HSCT
description Human adenovirus (HAdV) infection has an important clinical impact in the immunosuppressed population and is associated with high morbidity and mortality rates. The lack of a specific, safe and effective antiviral treatment against HAdV makes necessary the search for new therapeutic options. The aim of this study was to evaluate the in vitro activity of ganciclovir (GCV) against HAdV in co-infection by human cytomegalovirus (HCMV) and HAdV in cellular cultures. Quantitative real-time polymerase chain reaction (qPCR) was used to measure HAdV and HCMV DNA replication efficiency in monocultures and in co-infection situations in the presence of both cidofovir (CDV) and GCV. The effects of GCV and CDV were also evaluated in a burst assay (used to measure the production of virus particles) for both viruses, alone and in combination. GCV decreased by 1-log the HAdV DNA replication efficiency in co-infection with HCMV compared with its activity in HAdV monoculture. The burst assay showed that the reductions in virus yield in the presence of GCV were higher for HCMV and co-infection than for HAdV in monoculture (145.2±35.5- vs. 116.4±27.3- vs. 23.0±10.0-fold, respectively, P<0.05). The improved anti-HAdV activity of GCV during co-infection may be because of the more efficient phosphorylation of GCV by the HCMV protein kinase, UL97. Patients treated with GCV as pre-emptive therapy for HCMV infection may be considered as low-risk for developing HAdV infections; however, further evaluations are required to confirm these results.
publishDate 2020
dc.date.none.fl_str_mv 2020
2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/231344
url http://hdl.handle.net/10261/231344
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/BIO2015-68990-REDT
http://doi.org/10.1016/j.ijantimicag.2020.106046
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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