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Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with
Suzanne D Vernon1, Toni Whistler, Barbara Cameron
1Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. svernon@cdc.gov
Background:
Acute infectious diseases are typically accompanied by non-specific symptoms including fever, malaise, irritability and somnolence that usually resolve on recovery. However, in some individuals these symptoms persist in what is commonly termed post-infective fatigue. The objective of this pilot study was to determine the gene expression correlates of post-infective fatigue following acute Epstein Barr virus (EBV) infection.
Methods:
We followed 5 people with acute mononucleosis who developed post-infective fatigue of more than 6 months duration and 5 HLA-matched control subjects who recovered within 3 months. Subjects had peripheral blood mononuclear cell (PBMC) samples collected at varying time points including at diagnosis, then every 2 weeks for 3 months, then every 3 months for a year. Total RNA was extracted from the PBMC samples and hybridized to microarrays spotted with 3,800 oligonucleotides.
Results:
Those who developed post-infective fatigue had gene expression profiles indicative of an altered host response during acute mononucleosis compared to those who recovered uneventfully. Several genes including ISG20 (interferon stimulated gene), DNAJB2 (DnaJ [Hsp40] homolog and CD99), CDK8 (cyclin-dependent kinase 8), E2F2 (E2F transcription factor 2), CDK8 (cyclin-dependent kinase 8), and ACTN2 (actinin, alpha 2), known to be regulated during EBV infection, were differentially expressed in post-infective fatigue cases. Several of the differentially expressed genes affect mitochondrial functions including fatty acid metabolism and the cell cycle.
Conclusion:
These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.
Insights
Post-infective fatigue following Epstein-Barr virus (EBV) infection is linked to altered gene expression. Key genes involved in immune response and mitochondrial function were differentially expressed in patients with persistent fatigue.
Area of Science:
- Immunology
- Molecular Biology
- Genetics
Background:
- Acute infectious diseases often cause temporary symptoms like fever and fatigue.
- Post-infective fatigue can persist long-term in some individuals after recovery.
- Epstein-Barr virus (EBV) infection is a common cause of infectious mononucleosis and can lead to persistent fatigue.
Purpose of the Study:
- To investigate gene expression differences in individuals experiencing post-infective fatigue after EBV infection.
- To identify potential molecular correlates of persistent fatigue following acute mononucleosis.
Main Methods:
- A pilot study involving 5 patients with post-infective fatigue (duration >6 months) and 5 matched controls.
- Collection of peripheral blood mononuclear cell (PBMC) samples over a year.
- Gene expression profiling using microarrays on extracted RNA.
Main Results:
- Individuals with post-infective fatigue exhibited distinct gene expression profiles during acute infection compared to recovered controls.
- Differential expression of genes such as ISG20, DNAJB2, CDK8, E2F2, and ACTN2 was observed.
- Affected genes are involved in immune response, cell cycle regulation, and mitochondrial functions like fatty acid metabolism.
Conclusions:
- Preliminary findings suggest altered gene transcription patterns are associated with post-infective fatigue after EBV.
- These gene expression changes may offer insights into the mechanisms underlying persistent fatigue.
- Further research is warranted to explore these molecular alterations and their clinical implications.
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