Human Herpes Virus 6 (HHV-6) - Pathogen or Passenger? A pilot study of clinical laboratory data and next generation sequencing

Abstract

BackgroundHuman herpes virus 6 (HHV-6) is a ubiquitous organism that can cause a variety of clinical syndromes ranging from short-lived rash and fever through to life-threatening encephalitis.ObjectivesWe set out to generate observational data regarding the epidemiology of HHV-6 infection in clinical samples from a UK teaching hospital and to compare different diagnostic approaches.Study designFirst, we scrutinized HHV-6 detection in samples submitted to our hospital laboratory through routine diagnostic pathways. Second, we undertook a pilot study using Illumina next generation sequencing (NGS) to determine the frequency of HHV-6 in CSF and respiratory samples that were initially submitted to the laboratory for other diagnostic tests.ResultsOf 72 samples tested for HHV-6 by PCR at the request of a clinician, 24 (33%) were positive for HHV-6. The majority of these patients were under the care of the haematology team (30/41, 73%), and there was a borderline association between HHV-6 detection and both Graft versus Host Disease (GvHD) and Central nervous system (CNS) disease (p=0.05 in each case). We confirmed detection of HHV-6 DNA using NGS in 4/20 (20%) CSF and respiratory samples.ConclusionsHHV-6 is common in clinical samples submitted from a high-risk haematology population, and enhanced screening of this group should be considered. NGS can be used to identify HHV-6 from a complex microbiomee, but further controls are required to define the sensitivity and specificity, and to correlate these results with clinical disease. Our results underpin ongoing efforts to develop NGS technology for viral diagnostics.

Herpesvirus Infections of the Central Nervous System

“…93,95 However, a recent study incorporating metagenomic next-generation sequencing (mNGS) suggests that HHV-6A may be underdiagnosed by current molecular methods. 96 HHV-6 may be transmitted through respiratory secretions or saliva. As with other herpesviruses, HHV-6A and -6B are seen to result in latent infection, and therefore infection may be considered lifelong.…”

Human Herpesvirus Sequencing in the Genomic Era: The Growing Ranks of the Herpetic Legion

“…It also suggests a way forward for RNA-seq-based diagnostic studies which detect human herpesviruses within their datasets and hope to distinguish bystander or latent infections from high-level reactivation that is more likely to be associated with disease [78]. Sensitivity and specificity issues currently make introducing metagenomic sequencing for HHV6A/B detection and monitoring into the clinic challenging [79].…”