ArticleProceedings of the National Academy of Sciences of the United States of America2018
miRNA-mediated targeting of human cytomegalovirus reveals biological host and viral targets of IE2.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- Antiviral Approach to Cytomegalovirus Infection: An Overview of Conventional and Novel Strategies.Microorganisms · 2023Review
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- Article
- Myeloid cell tropism enables MHC-E-restricted CD8Science immunology · 2022Article
- Human MicroRNAs Attenuate the Expression of Immediate Early Proteins and HCMV Replication during Lytic and Latent Infection in Connection with Enhancement of Phosphorylated RelA/p65 (Serine 536) That Binds to MIEP.International journal of molecular sciences · 2022Article
- Review
- Virus, Exosome, and MicroRNA: New Insights into Autophagy.Advances in experimental medicine and biology · 2022Article
- Cytomegaloviral determinants of CD8Science immunology · 2021Article
- Hematopoietic cell-mediated dissemination of murine cytomegalovirus is regulated by NK cells and immune evasion.PLoS pathogens · 2021Article
- Insight for Immunotherapy of HCMV Infection.International journal of biological sciences · 2021Review
- Autophagy in Viral Development and Progression of Cancer.Frontiers in oncology · 2021Review
- Regulation of the MIE Locus During HCMV Latency and Reactivation.Pathogens (Basel, Switzerland) · 2020Review
- CD46 facilitates entry and dissemination of human cytomegalovirus.Nature communications · 2019Article
- Human cytomegalovirus genomics and transcriptomics through the lens of next-generation sequencing: revision and future challenges.Virus genes · 2019Review
- Expression of human miR-200b-3p and -200c-3p in cytomegalovirus-infected tissues.Bioscience reports · 2018Article
- Going live: How microRNAs might bring living vaccines back into the fold.Nature medicine · 2018Article
- Absence of IL-10 production by human PBMCs co-cultivated with human cells expressing or secreting retroviral immunosuppressive domains.PloS one · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Human cytomegalovirus (HCMV) impacts more than one-half of the human population owing to its capacity to manipulate the cell and create latent reservoirs in the host. Despite an extensive understanding of HCMV biology during acute infection in fibroblasts, the molecular basis for latency in myeloid cells remains incomplete. This knowledge gap is due largely to the fact that the existing genetic systems require virus rescue in fibroblasts, precluding the study of genes that are essential during acute infection, yet likely play unique roles in myeloid cells or the establishment of latency. Here we present a solution to address this restriction. Through the exploitation of a hematopoietic-specific microRNA, we demonstrate a one-step recombineering approach that enables gene silencing only in cells associated with latency. As a proof of concept, here we describe a TB40/E variant that undergoes hematopoietic targeting of the Immediate Early-2 (IE2) gene to explore its function during infection of myeloid cells. While virus replication of the hematopoietic-targeted IE2 variant was unimpaired in fibroblasts, we observed a >100-fold increase in virus titers in myeloid cells. Virus replication in myeloid cells demonstrated that IE2 has a significant transcriptional footprint on both viral and host genes. These data implicate IE2 as an essential mediator of virus biology in myeloid cells and illustrate the utility of cell-specific microRNA-based targeting.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.