Tissue specific signature of HHV-6 infection in ME/CFS.

Abstract

First exposure to various human herpesviruses (HHVs) including HHV-6, HCMV and EBV does not cause a life-threatening disease. In fact, most individuals are  frequently unaware of their first exposure to such pathogens. These herpesviruses  acquire lifelong latency in the human body where they show minimal genomic  activity required for their survival. We hypothesized that it is not the latency  itself but a timely, regionally restricted viral reactivation in a sub-set of  host cells that plays a key role in disease development. HHV-6 (HHV-6A and  HHV-6B) and HHV-7 are unique HHVs that acquire latency by integration of the  viral genome into sub-telomeric region of human chromosomes. HHV-6 reactivation  has been linked to Alzheimer's Disease, Chronic Fatigue Syndrome, and many other  diseases. However, lack of viral activity in commonly tested biological materials  including blood or serum strongly suggests tissue specific localization of active  HHV-6 genome. Here in this paper, we attempted to analyze active HHV-6  transcripts in postmortem tissue biopsies from a small cohort of ME/CFS patients  and matched controls by fluorescence in situ hybridization using a probe against  HHV-6 microRNA (miRNA), miR-aU14. Our results show abundant viral miRNA in  various regions of the human brain and associated neuronal tissues including the  spinal cord that is only detected in ME/CFS patients and not in controls. Our  findings provide evidence of tissue-specific active HHV-6 and EBV infection in  ME/CFS, which along with recent work demonstrating a possible relationship  between herpesvirus infection and ME/CFS, provide grounds for renewed discussion  on the role of herpesviruses in ME/CFS.