TY - JOUR
T1 - HHV-6 encoded small non-coding RNAs define an intermediate and early stage in viral reactivation
AU - Prusty, Bhupesh K
AU - Gulve, Nitish
AU - Chowdhury, Suvagata Roy
AU - Schuster, Michael
AU - Strempel, Sebastian
AU - Descamps, Vincent
AU - Rudel, Thomas
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
UR - https://www-scopus-com.db.rsu.lv/record/display.uri?eid=2-s2.0-85052997855&origin=resultslist&sort=plf-f&src=s&sid=387bdf500f42d2a240ffad0bddb0e180&sot=b&sdt=b&s=TITLE%28HHV-6+encoded+small+non-coding+RNAs+define+an+intermediate+and+early+stage+in+viral+reactivation%29&sl=103&sessionSearchId=387bdf500f42d2a240ffad0bddb0e180&relpos=0
U2 - 10.1038/s41525-018-0064-5
DO - 10.1038/s41525-018-0064-5
M3 - Article
C2 - 30210807
SN - 2056-7944
VL - 3
SP - 1
EP - 10
JO - npj Genomic Medicine
JF - npj Genomic Medicine
IS - 1
M1 - 25
ER -