Neuronal miR-138 Represses HSV-2 Lytic Infection by Regulating Viral and Host Genes with Mechanistic Differences from HSV-1

Self Cite

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.

Section: Cellular Mirnas Directly Targeting Viral Lytic Transcriptsmentioning

confidence: 92%

Section: Cellular Mirnas Repressing Cellular Pathways Important For V...mentioning

confidence: 99%

MicroRNA Regulation of Human Herpesvirus Latency

Chen

Deng

Pan

2022

Self Cite

“…Host microRNAs also regulate lytic replication and latency in a similar manner, restricting viral IE gene expression (Figure 2A) [64]. The neuron-specific microRNA miR-138-5p represses the expression of ICP0 of both HSV-1 and HSV-2 [65,66]. miR-138-5p also restricts the expression of host transcription factors Oct-1 and FOXC1, both of which promote viral replication [67].…”

Section: Hsv-1 Lifecycle: Latent Infectionmentioning

confidence: 98%

Models of Herpes Simplex Virus Latency

Canova,

Charron,

Leib

2024

Our current understanding of HSV latency is based on a variety of clinical observations, and in vivo, ex vivo, and in vitro model systems, each with unique advantages and drawbacks. The criteria for authentically modeling HSV latency include the ability to easily manipulate host genetics and biological pathways, as well as mimicking the immune response and viral pathogenesis in human infections. Although realistically modeling HSV latency is necessary when choosing a model, the cost, time requirement, ethical constraints, and reagent availability are also equally important. Presently, there remains a pressing need for in vivo models that more closely recapitulate human HSV infection. While the current in vivo, ex vivo, and in vitro models used to study HSV latency have limitations, they provide further insights that add to our understanding of latency. In vivo models have shed light on natural infection routes and the interplay between the host immune response and the virus during latency, while in vitro models have been invaluable in elucidating molecular pathways involved in latency. Below, we review the relative advantages and disadvantages of current HSV models and highlight insights gained through each.

“…In a recent study, it was reported that host miR-138 promotes HSV-1 latency by targeting the host OCT-1 and FOXC1 genes as well as the viral ICP0 gene [ 58 ]. However, during HSV-2 infection, the host miR-138 regulates the OCT-1, FOXC1, and viral ICP0 genes, as well as UL19 and UL20 genes, suggesting that alpha herpesviruses have evolved to exploit the neuronal miRNAs in order to promote viral latency [ 59 ]. Similarly, neurons expressing miR-138 target ICP0, the trans-activator of viral lytic gene.…”

Section: Mirna and Herpes Virusmentioning

confidence: 99%

miRNAs in Herpesvirus Infection: Powerful Regulators in Small Packages

Dass

Dhotre

Chakraborty

et al. 2023

microRNAs are a class of small, single-stranded, noncoding RNAs that regulate gene expression. They can be significantly dysregulated upon exposure to any infection, serving as important biomarkers and therapeutic targets. Numerous human DNA viruses, along with several herpesviruses, have been found to encode and express functional viral microRNAs known as vmiRNAs, which can play a vital role in host–pathogen interactions by controlling the viral life cycle and altering host biological pathways. Viruses have also adopted a variety of strategies to prevent being targeted by cellular miRNAs. Cellular miRNAs can act as anti- or proviral components, and their dysregulation occurs during a wide range of infections, including herpesvirus infection. This demonstrates the significance of miRNAs in host herpesvirus infection. The current state of knowledge regarding microRNAs and their role in the different stages of herpes virus infection are discussed in this review. It also delineates the therapeutic and biomarker potential of these microRNAs in future research directions.