Abstract

Human cytomegalovirus (HCMV) establishes either a latent (non-productive) or lytic (productive) infection depending upon cell type, cytokine milieu and the differentiation status of the infected cell. Undifferentiated cells, such as precursor cells of the myeloid lineage, support a latent infection whereas terminally differentiated cells, such as monocytes or dendritic cells are an environment conducive to reactivation and support a lytic infection. The mechanisms which regulate HCMV in either a latent or lytic infection have been the focus of intense investigation with a view to developing novel treatments for HCMV-associated disease which can have a heavy clinical burden after reactivation or primary infection in, especially, the immune compromised. To this end, a number of studies have been carried out in an unbiased manner to address global changes occurring within the latently infected cell to address the molecular changes associated with HCMV latency. In this review, we will concentrate on the proteomic analyses which have been carried out in undifferentiated myeloid cells which either stably express specific viral latency associated genes in isolation or on cells which have been latently infected with virus.

Highlights

  • Human cytomegalovirus (HCMV) is a species-specific pathogen which is carried by approximately60–80% of the population, depending on demographics [1]

  • Latently infected cells can be killed by targeting latency-associated changes in cellular proteins or killed by targeting the viral protein expressed during latency directly

  • Other identified changes have highlighted mechanisms used during latency to optimize conditions for the virus, such as regulation of cellular genes S100A8/A9 and Haematopoietic lineage cell-specific protein 1 (HCLS1)

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Summary

Introduction

Human cytomegalovirus (HCMV) is a species-specific pathogen which is carried by approximately. Front-line anti-virals for HCMV are limited due to poor bioavailability and drug resistance. Currently available drugs target the lytic phase of infection rather than the latent phase (the phases of the lifecycle are described in detail below) [2,3]. We will discuss how understanding the cellular changes which occur during latency, by studying the latency-induced proteome, may lead to an enhanced understanding of the mechanisms of viral latency and reactivation and aid the development of novel therapeutics to target the latent virus reservoir. Other identified changes have highlighted mechanisms used during latency to optimize conditions for the virus, such as regulation of cellular genes S100A8/A9 and HCLS1

HCMV Lytic and Latent Lifecycle
Viral Gene Expression during HCMV Latency
Cellular Transcriptome Analysis of HCMV Latency
Studying the Proteome
Total Proteomic Changes during HCMV Latency
Concluding Remarks
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