Profiling whole-tissue metabolic reprogramming during cutaneous poxvirus infection and clearance
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Published on: April 13, 2009
Luxin Pei1, Kirsten E Overdahl2, John P Shannon1
1Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Importance:
Human poxvirus infections have caused significant public health burdens both historically and recently during the unprecedented global Mpox virus outbreak. Although vaccinia virus (VACV) infection of mice is a commonly used model to explore the anti-poxvirus immune response, little is known about the metabolic changes that occur in vivo during infection. We hypothesized that the metabolome of VACV-infected skin would reflect the increased energetic requirements of both virus-infected cells and immune cells recruited to sites of infection. Therefore, we profiled whole VACV-infected skin using untargeted mass spectrometry to define the metabolome during infection, complementing these experiments with flow cytometry and transcriptomics. We identified specific metabolites, including nucleotides, itaconic acid, and glutamine, that were differentially expressed during VACV infection. Together, this study offers insight into both virus-specific and immune-mediated metabolic pathways that could contribute to the clearance of cutaneous poxvirus infection.
Insights
This study reveals metabolic shifts during vaccinia virus (VACV) skin infection in mice. Key metabolites like nucleotides and glutamine change, offering insights into host defense against poxviruses.
Area of Science:
- Virology
- Immunology
- Metabolomics
Background:
- Human poxvirus infections, including Mpox, pose significant public health challenges.
- The vaccinia virus (VACV) mouse model is crucial for studying anti-poxvirus immunity.
- Metabolic changes during VACV skin infection in vivo are poorly understood.
Purpose of the Study:
- To investigate the in vivo metabolic alterations in skin during VACV infection.
- To identify key metabolites associated with host response and viral clearance.
Main Methods:
- Untargeted mass spectrometry profiling of VACV-infected mouse skin.
- Complementary analyses using flow cytometry and transcriptomics.
Main Results:
- VACV infection significantly alters the skin metabolome.
- Differential expression of nucleotides, itaconic acid, and glutamine was observed.
- Metabolic pathways reflect increased energy demands of infected and immune cells.
Conclusions:
- The study elucidates virus-specific and immune-mediated metabolic pathways during cutaneous poxvirus infection.
- Identified metabolites may play a role in the clearance of poxvirus infections.
- Findings contribute to understanding host-pathogen metabolic interactions.
