Profiling the Blood Compartment of Hematopoietic Stem Cell Transplant Patients During Human Cytomegalovirus Reactivation.

blood compartment hematopoietic stem cell transplantation human cytomegalovirus peripheral blood mononuclear cell reactivation

Journal

Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359

Informations de publication

Date de publication:
2020
Historique:
received: 17 09 2020
accepted: 27 11 2020
entrez: 25 1 2021
pubmed: 26 1 2021
medline: 22 6 2021
Statut: epublish

Résumé

Human cytomegalovirus (HCMV) is a widespread pathogen establishing a latent infection in its host. HCMV reactivation is a major health burden in immunocompromised individuals, and is a major cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). Here we determined HCMV genomic levels using droplet digital PCR in different peripheral blood mononuclear cell (PBMC) populations in HCMV reactivating HSCT patients. This high sensitivity approach revealed that all PBMC populations harbored extremely low levels of viral DNA at the peak of HCMV DNAemia. Transcriptomic analysis of PBMCs from high-DNAemia samples revealed elevated expression of genes typical of HCMV specific T cells, while regulatory T cell enhancers as well as additional genes related to immune response were downregulated. Viral transcript levels in these samples were extremely low, but remarkably, the detected transcripts were mainly immediate early viral genes. Overall, our data indicate that HCMV DNAemia is associated with distinct signatures of immune response in the blood compartment, however it is not necessarily accompanied by substantial infection of PBMCs and the residual infected PBMCs are not productively infected.

Identifiants

pubmed: 33489936
doi: 10.3389/fcimb.2020.607470
pmc: PMC7820775
doi:

Substances chimiques

DNA, Viral 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

607470

Informations de copyright

Copyright © 2021 Bernshtein, Nachshon, Shnayder, Stern, Avdic, Blyth, Gottlieb, Abendroth, Slobedman, Stern-Ginossar and Schwartz.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Biana Bernshtein (B)

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Aharon Nachshon (A)

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Miri Shnayder (M)

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Lauren Stern (L)

Discipline of Infectious Diseases and Immunology, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia.

Selmir Avdic (S)

Sydney Cellular Therapies Laboratory, Westmead Institute for Medical Research, Westmead, NSW, Australia.

Emily Blyth (E)

Sydney Cellular Therapies Laboratory, Westmead Institute for Medical Research, Westmead, NSW, Australia.
BMT and Cell Therapies Unit, Westmead Hospital, Sydney, NSW, Australia.
Westmead Institute for Medical Research at the University of Sydney, Westmead, NSW, Australia.
Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.

David Gottlieb (D)

BMT and Cell Therapies Unit, Westmead Hospital, Sydney, NSW, Australia.
Westmead Institute for Medical Research at the University of Sydney, Westmead, NSW, Australia.
Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia.

Allison Abendroth (A)

Discipline of Infectious Diseases and Immunology, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia.

Barry Slobedman (B)

Discipline of Infectious Diseases and Immunology, Faculty of Medicine and Health, Charles Perkins Centre, University of Sydney, Camperdown, NSW, Australia.

Noam Stern-Ginossar (N)

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

Michal Schwartz (M)

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel.

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