Molecular Markers of EBV- and HHV6-Associated Mononucleosis

Abstract

Epstein-Barr virus (EBV) and human herpesvirus type 6 (HHV6) are causative agents of infectious mononucleosis and can lead to the development of lymphoproliferative diseases. Means of radical therapy for this disease are yet to be found. Key transcripts involved in the pathogenesis can be used as molecular markers and also as potential therapeutic targets. The aim of the study was to identify molecular markers associated with infection caused by EBV and HHV6; specifically, we looked into the markers localized in blood leukocytes of patients with infectious mononucleosis. Materials and Methods. We studied the transcriptome of peripheral blood leukocytes in children and adolescents with infectious mononucleosis caused by Epstein-Barr virus (EBV-IM) and human herpesvirus type 6 (HHV6-IM), as well as healthy subjects matched by gender and age. Using our original DNA biochips, we determined the expression of 403 genes (total representation level of all mRNA of one gene) and 712 transcripts (individual spliced mRNA of one gene) essential for the proliferation and apoptosis of immunocompetent cells. Data analysis was performed using a combination of machine learning and traditional statistics. The genes and transcripts which are highly important for paired classification and have the statistically significant differences in the expression between patients and healthy subjects were selected to serve molecular markers of the infection. Results. Unique groups of candidate markers for EBV-IM and HHV6-IM were identified. EBV-IM was characterized by a decreased expression of the AR transcript 5 and ASCC1 transcript 4 and also of the CAD gene and FADD mRNA; an increased expression of the HLA-DPA1 transcript 2 and RIPK1 transcript 4 were found. In patients with HHV6-IM, an increase in the expression of AVEN mRNA, CHUK transcript 2, CIRBP transcript 2, and TRAF3 transcript 2, as well as a decrease in the expression of IRAK4 transcript 10 was observed. In the post-infection period, the expression levels of most of the markers returned to normal. Conclusion. The sets of identified markers are uniquely characteristic of the two infections (EBV-IM and HHV6-IM) and can be used as targets for new therapies.