Molecular characterization of human cytomegalovirus infection with single-cell transcriptomics

Schwartz, Michal; Shnayder, Miri; Nachshon, Aharon; Arazi, Tamar; Kitsberg, Yaarit; Samia, Roi Levi; Lavi, Michael; Kuint, Rottem; Tsabari, Reuven; Stern-Ginossar, Noam

doi:10.1038/s41564-023-01325-x

Cited by 18 publications

(15 citation statements)

References 58 publications

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“…CMV infection induces a systemic inflammatory response characterized by the recruitment of neutrophils and activation of macrophages [ 6 , 25 , 26 ]. We observed a significant expansion of CD11b+F4/80+ macrophages (gated on Ly6G- cells) and CD11b+Ly6G+ neutrophils in the lung BAL fluid following MCMV infection.…”

Section: Resultsmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling Pathway

Chen,

et al. 2024

Viruses

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Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.

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Section: Resultsmentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling Pathway

Chen,

et al. 2024

Viruses

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“…These clinical observations imply that HCMV does not reside solely in the bone marrow, and that there are likely additional sources of HCMV that reside within tissues. In support of this possibility, we recently showed that monocyte‐derived macrophages can be infected in a latent‐like manner, in which viral gene expression is repressed, but the HCMV genome is maintained and can reactivate 34 . Nevertheless, it remains possible that the evidence from the clinic for tissue‐resident source of HCMV reactivation is in fact due to constant low level and subclinical persistent infection that is kept under control by the immune system.…”

Section: Hcmv Reactivation In the Clinicmentioning

confidence: 99%

“…In support of this possibility, we recently showed that monocyte-derived macrophages can be infected in a latent-like manner, in which viral gene expression is repressed, but the HCMV genome is maintained and can reactivate. 34 Nevertheless, it remains possible that the evidence from the clinic for tissue-resident source of HCMV reactivation is in fact due to constant low level and subclinical persistent infection that is kept under control by the immune system. As discussed below, at least in the murine model, there is no clear evidence for ongoing viral persistence.…”

Section: Hcmv Reactivation In the Clinicmentioning

confidence: 99%

Rethinking human cytomegalovirus latency reservoir

Schwartz

Stern-Ginossar

2023

Annals of the New York Academy of Sciences

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Human cytomegalovirus (HCMV) is a prevalent herpesvirus, infecting the majority of the human population. Like other herpesviruses, it causes lifelong infection through the establishment of latency. Although reactivation from latency can cause significant morbidity and mortality in immunocompromised hosts, our understanding of HCMV latency and how it is maintained remains limited. Here, we discuss the characterized latency reservoir in hematopoietic cells in the bone marrow and the gaps in our knowledge of mechanisms that facilitate HCMV genome maintenance in dividing cells. We further review clinical evidence that strongly suggests the tissue origin of HCMV reactivation, and we outline similarities to murine cytomegalovirus where latency in tissue‐resident cells has been demonstrated. Overall, we think these observations call for a rethinking of HCMV latency reservoirs and point to potential sources of HCMV latency that reside in tissues.

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“…Undoubtedly, innate immunity-mediated by macrophages and natural killer cells (NK) plays pivotal roles in protecting organisms from virus infections and tumor treatment. [42][43][44] Therefore, the effects of the developed Se@PEDV nanovaccine on innate immunity were first evaluated. Intriguingly, it was found that Se@PEDV nanovaccine could significantly enhance the phagocytosis capability of the peritoneal macrophages which engulfing much more fluorescence polystyrene beads (50 nm) than other immunizations (Figure 4b,c).…”

Section: Se@pdnv Nanovaccine Elicited Robust Cellular and Humoral Imm...mentioning

confidence: 99%

Designing Selenium Nanoadjuvant as Universal Agent for Live‐Killed Virus‐Based Vaccine

Deng

Wang

et al. 2023

Small Methods

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Inactivated virus vaccines with whole antigen spectra and good safety are the commonly used modality for preventing infections. However, the poor immunogenicity greatly limits its clinical applications. Herein, by taking advantages of the crucial roles of Se in the functions of immune cells and its biomineralization property, it successfully in‐situ synthesized Se nanoadjuvant on inactivated viruses such as porcine epidemic diarrhea virus (PEDV), pseudorabies virus (PRV), and porcine reproductive and respiratory syndrome virus (PRRSV) in a facile method, which is universal to construct other inactivated virus vaccines. The nanovaccine can highly effectively enhance the uptake of PEDV/PRV/PRRSV into dendritic cells (DCs) and activate DCs via triggering TLR4 signaling pathways and regulating selenoproteins expressions. Furthermore, it exhibited better activities in triggering macrophages and natural killer cells‐mediated innate immunity and T cells‐mediated cellular immunity compared to PEDV and the commercial inactivated PEDV vaccine on both mice and swine models. This study provides a universal Se nanoadjuvant for developing inactivated viruses‐based nanovaccines for preventing virus infections.

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Molecular characterization of human cytomegalovirus infection with single-cell transcriptomics

Cited by 18 publications

References 58 publications

Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling Pathway

Mesenchymal Stem Cell-Derived Exosomes Attenuate Murine Cytomegalovirus-Infected Pneumonia via NF-κB/NLRP3 Signaling Pathway

Rethinking human cytomegalovirus latency reservoir

Designing Selenium Nanoadjuvant as Universal Agent for Live‐Killed Virus‐Based Vaccine

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