Characterization of human cytomegalovirus infection dynamics in human microglia
Human cytomegalovirus (HCMV) is a β-herpesvirus that establishes asymptomatic infections in immunocompetent individuals but can cause severe or even life-threatening symptoms in immunocompromised patients. HCMV can replicate in a wide variety of cells through the engagement of diverse cell factors w...
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/389177 |
| Acceso en línea: | http://hdl.handle.net/10261/389177 https://api.elsevier.com/content/abstract/scopus_id/105004006061 |
| Access Level: | acceso abierto |
| Palabra clave: | Tropism Antibodies Entry inhibitors Human cytomegalovirus Microglia Neuropilin-2 (NRP-2) Cytomegalovirus |
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Characterization of human cytomegalovirus infection dynamics in human microgliaNuevalos Guaita, MarcosJimoh, Tajudeen O.Barrall, Emma B.Atanasoff, Kristina E.Ehrlich, Michelle E.Gandy, SamGarcía-Ríos, EstéfaniPerez Romero, PilarDuty, J. AndrewTortorella, DomenicoTropismAntibodiesEntry inhibitorsHuman cytomegalovirusMicrogliaNeuropilin-2 (NRP-2)CytomegalovirusHuman cytomegalovirus (HCMV) is a β-herpesvirus that establishes asymptomatic infections in immunocompetent individuals but can cause severe or even life-threatening symptoms in immunocompromised patients. HCMV can replicate in a wide variety of cells through the engagement of diverse cell factors with the viral envelope protein gH/gL/gO (trimer) or gH/gL/UL128/UL130/UL131a (pentamer), allowing for systemic spread within the human host. This study explores HCMV infection tropism and dynamics in human microglia, demonstrating the susceptibility of microglia to both clinical and laboratory HCMV strains, albeit with lower efficacy for the laboratory strain, implying that both the gH/gL-trimer and -pentamer can mediate virus entry in microglia. The importance of the gH/gL pentamer for virus entry was demonstrated by the inhibition of virus infection upon pre-incubation with a soluble neuropilin-2 (NRP-2) entry factor. Further, we demonstrated that HCMV infection can be effectively inhibited by monoclonal antibodies specific for the gH/gL complexes and HCMV hyperimmunoglobulin. Lastly, we report that microglia infection can be prevented by newly characterized chemical entry inhibitors. Altogether, these findings underscore the potential of microglia as valuable models for studying HCMV neurotropism and strategies to block virus infection in cells that can impact neurological disorders.M.N. is supported by the FPU programprogramme (FPU19/05927), Spanish Ministry of Science, Innovation and University. E.G.R. is supported by the Generalitat Valenciana plan GenT (CIDEIG/2022/028). S.G. and M.E.E. were supported by U01AG046170, RF1AG058469, RF1AG059319, R01AG061894 and P30 AG066514 to Mary Sano, and Cure Alzheimer’s Fund. T.J., E.B.B., K.A., J.A.D. and D.T. were in part supported by the NIH Institutional Research Training Awards – T32-AI007647, AI R56174062, R01AI139258, R21AI147632, R56AI174062 and R56AI175974.Peer reviewedMicrobiology SocietyGeneralitat ValencianaMinisterio de Ciencia, Innovación y Universidades (España)Cure Alzheimer's FundNational Health Service (UK)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/389177https://api.elsevier.com/content/abstract/scopus_id/105004006061reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)InglésThe Journal of general virologyhttps://doi.org/10.1099/jgv.0.002096Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3891772026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Characterization of human cytomegalovirus infection dynamics in human microglia |
| title |
Characterization of human cytomegalovirus infection dynamics in human microglia |
| spellingShingle |
Characterization of human cytomegalovirus infection dynamics in human microglia Nuevalos Guaita, Marcos Tropism Antibodies Entry inhibitors Human cytomegalovirus Microglia Neuropilin-2 (NRP-2) Cytomegalovirus |
| title_short |
Characterization of human cytomegalovirus infection dynamics in human microglia |
| title_full |
Characterization of human cytomegalovirus infection dynamics in human microglia |
| title_fullStr |
Characterization of human cytomegalovirus infection dynamics in human microglia |
| title_full_unstemmed |
Characterization of human cytomegalovirus infection dynamics in human microglia |
| title_sort |
Characterization of human cytomegalovirus infection dynamics in human microglia |
| dc.creator.none.fl_str_mv |
Nuevalos Guaita, Marcos Jimoh, Tajudeen O. Barrall, Emma B. Atanasoff, Kristina E. Ehrlich, Michelle E. Gandy, Sam García-Ríos, Estéfani Perez Romero, Pilar Duty, J. Andrew Tortorella, Domenico |
| author |
Nuevalos Guaita, Marcos |
| author_facet |
Nuevalos Guaita, Marcos Jimoh, Tajudeen O. Barrall, Emma B. Atanasoff, Kristina E. Ehrlich, Michelle E. Gandy, Sam García-Ríos, Estéfani Perez Romero, Pilar Duty, J. Andrew Tortorella, Domenico |
| author_role |
author |
| author2 |
Jimoh, Tajudeen O. Barrall, Emma B. Atanasoff, Kristina E. Ehrlich, Michelle E. Gandy, Sam García-Ríos, Estéfani Perez Romero, Pilar Duty, J. Andrew Tortorella, Domenico |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Generalitat Valenciana Ministerio de Ciencia, Innovación y Universidades (España) Cure Alzheimer's Fund National Health Service (UK) Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Tropism Antibodies Entry inhibitors Human cytomegalovirus Microglia Neuropilin-2 (NRP-2) Cytomegalovirus |
| topic |
Tropism Antibodies Entry inhibitors Human cytomegalovirus Microglia Neuropilin-2 (NRP-2) Cytomegalovirus |
| description |
Human cytomegalovirus (HCMV) is a β-herpesvirus that establishes asymptomatic infections in immunocompetent individuals but can cause severe or even life-threatening symptoms in immunocompromised patients. HCMV can replicate in a wide variety of cells through the engagement of diverse cell factors with the viral envelope protein gH/gL/gO (trimer) or gH/gL/UL128/UL130/UL131a (pentamer), allowing for systemic spread within the human host. This study explores HCMV infection tropism and dynamics in human microglia, demonstrating the susceptibility of microglia to both clinical and laboratory HCMV strains, albeit with lower efficacy for the laboratory strain, implying that both the gH/gL-trimer and -pentamer can mediate virus entry in microglia. The importance of the gH/gL pentamer for virus entry was demonstrated by the inhibition of virus infection upon pre-incubation with a soluble neuropilin-2 (NRP-2) entry factor. Further, we demonstrated that HCMV infection can be effectively inhibited by monoclonal antibodies specific for the gH/gL complexes and HCMV hyperimmunoglobulin. Lastly, we report that microglia infection can be prevented by newly characterized chemical entry inhibitors. Altogether, these findings underscore the potential of microglia as valuable models for studying HCMV neurotropism and strategies to block virus infection in cells that can impact neurological disorders. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/389177 https://api.elsevier.com/content/abstract/scopus_id/105004006061 |
| url |
http://hdl.handle.net/10261/389177 https://api.elsevier.com/content/abstract/scopus_id/105004006061 |
| dc.language.none.fl_str_mv |
Inglés |
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Inglés |
| dc.relation.none.fl_str_mv |
The Journal of general virology https://doi.org/10.1099/jgv.0.002096 Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
| dc.publisher.none.fl_str_mv |
Microbiology Society |
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Microbiology Society |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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