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How Viral and Intracellular Bacterial Pathogens Reprogram the Metabolism of Host Cells to Allow Their Intracellular
Wolfgang Eisenreich1, Thomas Rudel2, Jürgen Heesemann3
1Chair of Biochemistry, Department of Chemistry, Technische Universität München, Garching, Germany.
Abstract:
Viruses and intracellular bacterial pathogens (IBPs) have in common the need of suitable host cells for efficient replication and proliferation during infection. In human infections, the cell types which both groups of pathogens are using as hosts are indeed quite similar and include phagocytic immune cells, especially monocytes/macrophages (MOs/MPs) and dendritic cells (DCs), as well as nonprofessional phagocytes, like epithelial cells, fibroblasts and endothelial cells. These terminally differentiated cells are normally in a metabolically quiescent state when they are encountered by these pathogens during infection. This metabolic state of the host cells does not meet the extensive need for nutrients required for efficient intracellular replication of viruses and especially IBPs which, in contrast to the viral pathogens, have to perform their own specific intracellular metabolism to survive and efficiently replicate in their host cell niches. For this goal, viruses and IBPs have to reprogram the host cell metabolism in a pathogen-specific manner to increase the supply of nutrients, energy, and metabolites which have to be provided to the pathogen to allow its replication. In viral infections, this appears to be often achieved by the interaction of specific viral factors with central metabolic regulators, including oncogenes and tumor suppressors, or by the introduction of virus-specific oncogenes. Less is so far known on the mechanisms leading to metabolic reprogramming of the host cell by IBPs. However, the still scant data suggest that similar mechanisms may also determine the reprogramming of the host cell metabolism in IBP infections. In this review, we summarize and compare the present knowledge on this important, yet still poorly understood aspect of pathogenesis of human viral and especially IBP infections.
Insights
Viruses and intracellular bacterial pathogens (IBPs) reprogram host cell metabolism for replication. This review compares how viruses and IBPs manipulate host cells, highlighting gaps in understanding IBP mechanisms.
Area of Science:
- Pathogen-host interactions
- Cellular metabolism
- Infectious disease pathogenesis
Background:
- Viruses and intracellular bacterial pathogens (IBPs) require host cells for replication.
- Common host cells include immune cells (monocytes/macrophages, dendritic cells) and nonprofessional phagocytes.
- Host cells are typically quiescent, lacking nutrients for pathogen growth.
Purpose of the Study:
- To summarize and compare knowledge on host cell metabolic reprogramming by viruses and IBPs.
- To highlight the importance of pathogen-induced metabolic changes in pathogenesis.
- To identify gaps in understanding IBP-mediated metabolic reprogramming.
Main Methods:
- Literature review and comparative analysis of existing studies.
- Synthesis of current knowledge on viral and IBP pathogenesis.
- Identification of common and distinct mechanisms of host cell manipulation.
Main Results:
- Both viruses and IBPs reprogram host cell metabolism to meet nutrient demands.
- Viruses often use viral factors interacting with host metabolic regulators or oncogenes.
- Mechanisms for IBP-induced metabolic reprogramming are less understood but may involve similar pathways.
Conclusions:
- Metabolic reprogramming is crucial for viral and IBP replication.
- Understanding these mechanisms is key to developing new therapeutic strategies.
- Further research is needed to elucidate IBP-specific metabolic reprogramming pathways.
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