Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with Epstein Barr virus

BMC Infect Dis. 2006 Jan 31;6:15. doi: 10.1186/1471-2334-6-15.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Cohort Studies
  • Fatigue / complications*
  • Fatigue / metabolism*
  • Fatigue / pathology
  • Fatigue / physiopathology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Infectious Mononucleosis / complications*
  • Infectious Mononucleosis / metabolism
  • Infectious Mononucleosis / pathology
  • Infectious Mononucleosis / physiopathology*
  • Male
  • Middle Aged
  • Mitochondria / metabolism*
  • Mitochondrial Diseases / complications*
  • Mitochondrial Diseases / metabolism*
  • Mitochondrial Diseases / pathology
  • Mitochondrial Diseases / physiopathology
  • Pilot Projects
  • Prospective Studies