Abstract

ABSTRACTHerpesvirus latency has been difficult to understand molecularly due to low levels of viral genomes and gene expression. In the case of the betaherpesvirus human cytomegalovirus (HCMV), this is further complicated by the heterogeneity inherent to hematopoietic subpopulations harboring genomes and, as a consequence, the various patterns of infection that simultaneously exist in a host, ranging from latent to lytic. Single-cell RNA sequencing (scRNA-seq) provides tremendous potential in measuring the gene expression profiles of heterogeneous cell populations for a wide range of applications, including in studies of cancer, immunology, and infectious disease. A recent study by Shnayder et al. (mBio 9:e00013-18, 2018, https://doi.org/10.1128/mBio.00013-18) utilized scRNA-seq to define transcriptomal characteristics of HCMV latency. They conclude that latency-associated gene expression is similar to the late lytic viral program but at lower levels of expression. The study highlights the numerous challenges, from the definition of latency to the analysis of scRNA-seq, that exist in defining a latent transcriptome.

Highlights

  • Herpesvirus latency has been difficult to understand molecularly due to low levels of viral genomes and gene expression

  • Herpesviruses are incurable due to their ability to establish a latent infection that cannot be targeted by current antivirals

  • Highly sensitive, global analysis of gene expression during infection with human cytomegalovirus (HCMV) in cell types supporting a latent infection paints a far more complex picture of viral gene expression associated with latent states [1,2,3,4,5]

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Summary

Introduction

Herpesvirus latency has been difficult to understand molecularly due to low levels of viral genomes and gene expression. To define viral genes associated with natural infection in the host, Shnayder et al searched the existing bank of transcriptome sequencing (RNA-seq) data for the presence of HCMV transcripts across human tissues [11].

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