Reanalysis of single-cell RNA sequencing data does not support herpes simplex virus 1 latency in non-neuronal ganglionic cells in mice.
Werner J D OuwendijkPavitra RoychoudhuryAnthony L CunninghamKeith R JeromeDavid M KoellePaul R KinchingtonIan MohrAngus C WilsonGeorges G M G M VerjansDaniel P DepledgePublished in: bioRxiv : the preprint server for biology (2023)
Most individuals are latently infected with herpes simplex virus type 1 (HSV-1) and it is well-established that HSV-1 establishes latency in sensory neurons of peripheral ganglia. However, it was recently proposed that latent virus is also present in immune cells recovered from ganglia in a mouse model used for studying latency. Here, we reanalyzed the single-cell RNA sequencing (scRNA-Seq) data that formed the basis for this conclusion. Unexpectedly, off-target priming in 3' scRNA-Seq experiments enabled the detection of non-polyadenylated HSV-1 latency-associated transcript ( LAT ) intronic RNAs. However, LAT reads were near-exclusively detected in a mixed population of cells undergoing cell death. Specific loss of HSV-1 LAT and neuronal transcripts during quality control filtering indicated widespread destruction of neurons, supporting the presence of contaminating cell-free RNA in other cells following tissue processing. In conclusion, the reported detection of latent HSV-1 in non-neuronal cells is best explained by inaccuracies in the data analyses.
Keyphrases
- herpes simplex virus
- single cell
- induced apoptosis
- cell cycle arrest
- rna seq
- cell death
- mouse model
- cell free
- endoplasmic reticulum stress
- type diabetes
- electronic health record
- genome wide
- high throughput
- spinal cord
- big data
- dna methylation
- cell proliferation
- oxidative stress
- adipose tissue
- machine learning
- spinal cord injury
- brain injury
- metabolic syndrome
- quantum dots
- subarachnoid hemorrhage
- high fat diet induced
- circulating tumor cells