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

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.

• Authors: Suzanne D Vernon, Toni Whistler, Barbara Cameron, Ian B Hickie, William C Reeves, Andrew Lloyd
• Journal: BMC infectious diseases (BMC Infect Dis) Vol. 6 Pg. 15 (Jan 31 2006) ISSN: 1471-2334 [Electronic] England
• PMID: 16448567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Topics

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