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Acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice

INTRODUCTION: Human cytomegalovirus (HCMV) infection in infants can lead to severe diseases, including neonatal hepatitis. The single-cell dimensional changes in immune cells after the initial CMV infection remain elusive, as do the effects of CMV infection on hepatic lipid metabolism. METHODS: We e...

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Autores principales: Gao, Juanzi, Wang, Anmin, Bu, Xiangyi, Jia, Weidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449610/
https://www.ncbi.nlm.nih.gov/pubmed/37638012
http://dx.doi.org/10.3389/fimmu.2023.1169869
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author Gao, Juanzi
Wang, Anmin
Bu, Xiangyi
Jia, Weidong
author_facet Gao, Juanzi
Wang, Anmin
Bu, Xiangyi
Jia, Weidong
author_sort Gao, Juanzi
collection PubMed
description INTRODUCTION: Human cytomegalovirus (HCMV) infection in infants can lead to severe diseases, including neonatal hepatitis. The single-cell dimensional changes in immune cells after the initial CMV infection remain elusive, as do the effects of CMV infection on hepatic lipid metabolism. METHODS: We employed single-cell RNA-sequencing to investigate the changes in liver cell types and immune responses in infant mice following murine CMV (MCMV) infection. Additionally, we examined alterations in protein expression profiles related to lipid metabolism in hepatocytes and the role of the key transcription factor PPAR-γ in hepatocytes during CMV infection. RESULTS: Our study revealed that MCMV infects most liver cell types in infant mice, leading to an increase in the proportion of proliferating CD8 effector T cells and a subset of Nos2(+) monocytes, potentially playing an essential role in early anti-viral responses. Furthermore, MCMV infection resulted in altered protein expression of lipid metabolism in hepatocytes. Knocking down the transcription factor PPAR-γ in hepatocytes effectively inhibited CMV infection. DISCUSSION: Our findings underscore the immune system's response to early-stage MCMV infection and the subsequent impact on hepatic lipid metabolism in infant mice. This research provides new insights into the mechanisms of CMV infection and could pave the way for novel therapeutic strategies.
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spelling pubmed-104496102023-08-26 Acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice Gao, Juanzi Wang, Anmin Bu, Xiangyi Jia, Weidong Front Immunol Immunology INTRODUCTION: Human cytomegalovirus (HCMV) infection in infants can lead to severe diseases, including neonatal hepatitis. The single-cell dimensional changes in immune cells after the initial CMV infection remain elusive, as do the effects of CMV infection on hepatic lipid metabolism. METHODS: We employed single-cell RNA-sequencing to investigate the changes in liver cell types and immune responses in infant mice following murine CMV (MCMV) infection. Additionally, we examined alterations in protein expression profiles related to lipid metabolism in hepatocytes and the role of the key transcription factor PPAR-γ in hepatocytes during CMV infection. RESULTS: Our study revealed that MCMV infects most liver cell types in infant mice, leading to an increase in the proportion of proliferating CD8 effector T cells and a subset of Nos2(+) monocytes, potentially playing an essential role in early anti-viral responses. Furthermore, MCMV infection resulted in altered protein expression of lipid metabolism in hepatocytes. Knocking down the transcription factor PPAR-γ in hepatocytes effectively inhibited CMV infection. DISCUSSION: Our findings underscore the immune system's response to early-stage MCMV infection and the subsequent impact on hepatic lipid metabolism in infant mice. This research provides new insights into the mechanisms of CMV infection and could pave the way for novel therapeutic strategies. Frontiers Media S.A. 2023-08-10 /pmc/articles/PMC10449610/ /pubmed/37638012 http://dx.doi.org/10.3389/fimmu.2023.1169869 Text en Copyright © 2023 Gao, Wang, Bu and Jia https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Gao, Juanzi
Wang, Anmin
Bu, Xiangyi
Jia, Weidong
Acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice
title Acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice
title_full Acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice
title_fullStr Acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice
title_full_unstemmed Acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice
title_short Acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice
title_sort acute murine cytomegalovirus infection boosts cell-type specific response and lipid metabolism changes in the liver of infant mice
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449610/
https://www.ncbi.nlm.nih.gov/pubmed/37638012
http://dx.doi.org/10.3389/fimmu.2023.1169869
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