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HHV-6 encoded small non-coding RNAs define an intermediate and early stage in viral reactivation.
Prusty, Bhupesh K Gulve, Nitish Chowdhury, Suvagata Roy Schuster, Michael Strempel, Sebastian Descamps, Vincent Rudel, Thomas
Prusty, Bhupesh K
Gulve, Nitish
Chowdhury, Suvagata Roy
Schuster, Michael
Strempel, Sebastian
Descamps, Vincent
Rudel, Thomas
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2018-01-01
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Abstract
Human herpesvirus 6A and 6B frequently acquires latency. HHV-6 activation has been associated with various human diseases. Germ line inheritance of chromosomally integrated HHV-6 makes viral DNA-based analysis difficult for determination of early stages of viral activation. We characterized early stages of HHV-6 activation using high throughput transcriptomics studies and applied the results to understand virus activation under clinical conditions. Using a latent HHV-6A cell culture model in U2OS cells, we identified an early stage of viral reactivation, which we define as transactivation that is marked by transcription of several viral small non-coding RNAs (sncRNAs) in the absence of detectable increase in viral replication and proteome. Using deep sequencing approaches, we detected previously known as well as a new viral sncRNAs that characterized viral transactivation and differentiated it from latency. Here we show changes in human transcriptome upon viral transactivation that reflect multiple alterations in mitochondria-associated pathways, which was supported by observation of increased mitochondrial fragmentation in virus reactivated cells. Furthermore, we present here a unique clinical case of DIHS/DRESS associated death where HHV-6 sncRNA-U14 was abundantly detected throughout the body of the patient in the presence of low viral DNA. In this study, we have identified a unique and early stage of viral activation that is characterized by abundant transcription of viral sncRNAs, which can serve as an ideal biomarker under clinical conditions.
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2056-7944
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Attribution-NonCommercial-ShareAlike 3.0 United States