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

Biana Bernshtein, Aharon Nachshon, Miri Shnayder, Lauren Stern, Selmir Avdic, Emily Blyth, David Gottlieb, Allison Abendroth, Barry Slobedman, Noam Stern-Ginossar, Michal Schwartz

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4 Scopus citations

Abstract

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.

Original languageEnglish
Article number607470
JournalFrontiers in Cellular and Infection Microbiology
Volume10
DOIs
StatePublished - 2020
Externally publishedYes

Bibliographical note

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

Keywords

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

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