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


CONCLUSIONS
These preliminary data provide insights into alterations in gene transcripts associated with the varied clinical outcomes from acute infectious mononucleosis.
Vernon
Suzanne D
SD
Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. svernon@cdc.gov
Whistler
Toni
T
Cameron
Barbara
B
Hickie
Ian B
IB
Reeves
William C
WC
Lloyd
Andrew
A
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D005221:Fatigue / Q000150:complications* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007244:Infectious Mononucleosis / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000150:complications* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010865:Pilot Projects; D011446:Prospective Studies