MicroRNA Regulation of Human Herpesvirus Latency

Abstract

Herpesviruses are ubiquitous human pathogens. After productive (lytic) infection, all human herpesviruses are able to establish life-long latent infection and reactivate from it. Latent infection entails suppression of viral replication, maintenance of the viral genome in infected cells, and the ability to reactivate. Most human herpesviruses encode microRNAs (miRNAs) that regulate these processes during latency. Meanwhile, cellular miRNAs are hijacked by herpesviruses to participate in these processes. The viral or cellular miRNAs either directly target viral transcripts or indirectly affect viral infection through host pathways. These findings shed light on the molecular determinants that control the lytic-latent switch and may lead to novel therapeutics targeting latent infection. We discuss the multiple mechanisms by which miRNAs regulate herpesvirus latency, focusing on the patterns in these mechanisms.

Keywords: EBV; HCMV; HSV; KSHV; herpesvirus; latency; microRNA; reactivation.

Figure 1

Genomic locations of human herpesvirus miRNAs. The locations of miRNA precursors are denoted by red triangles. Red characters indicate the miRNAs expressed during latent infection. Thick arrows along the genomes represent selected viral genes and the directions of transcription.

Figure 2

Direct targeting of viral IE genes by viral and cellular miRNAs. Blue rectangles represent viral miRNAs, and yellow rectangles represent host ones.

Figure 3

Regulation of apoptosis pathways by viral and cellular miRNAs. The genes directly targeted by miRNAs are indicated by orange rectangles. Green patterns represent protein modification. Some graphic elements were obtained from Servier Medical Art (SMART) (https://smart.servier.com/ (accessed on 12 May 2022)).

Figure 4

Regulation of host immune pathways by viral and cellular miRNAs. The genes directly targeted by miRNA are indicated by orange rectangles or characters. The red and green characters represent host and viral miRNAs, respectively. Some graphic elements were obtained from Servier Medical Art (SMART) (https://smart.servier.com/ (accessed on 12 May 2022)).