Regulation of the Host Antiviral State by Intercellular Communications.

Sonia Assil,Brian Webster,Marlène Dreux

doi:10.3390/v7082840

Abstract

Viruses usually induce a profound remodeling of host cells, including the usurpation of host machinery to support their replication and production of virions to invade new cells. Nonetheless, recognition of viruses by the host often triggers innate immune signaling, preventing viral spread and modulating the function of immune cells. It conventionally occurs through production of antiviral factors and cytokines by infected cells. Virtually all viruses have evolved mechanisms to blunt such responses. Importantly, it is becoming increasingly recognized that infected cells also transmit signals to regulate innate immunity in uninfected neighboring cells. These alternative pathways are notably mediated by vesicular secretion of various virus- and host-derived products (miRNAs, RNAs, and proteins) and non-infectious viral particles. In this review, we focus on these newly-described modes of cell-to-cell communications and their impact on neighboring cell functions. The reception of these signals can have anti- and pro-viral impacts, as well as more complex effects in the host such as oncogenesis and inflammation. Therefore, these “broadcasting” functions, which might be tuned by an arms race involving selective evolution driven by either the host or the virus, constitute novel and original regulations of viral infection, either highly localized or systemic.

Highlights

Intercellular transfer of materials to neighboring cells by extracellular vesicles is increasingly recognized as an important mean of communication between cells [1]
Innate immunity represents the first line of defense against viral infections, implying that viral persistence requires the virus to evade and/or inhibit this host response
As discussed in this review, aside from the activation by infectious viral particles, recent work illustrates the existence of alternative sensing mechanisms of infected cells by neighboring cells that likely constitutes an important aspect of innate immunity

Summary

Introduction

Intercellular transfer of materials to neighboring cells by extracellular vesicles is increasingly recognized as an important mean of communication between cells [1]. Host cells trigger signaling events that lead to the activation of an innate immune response, characterized by the secretion of interferons (IFNs) and the expression of an array of antiviral factors, including IFN-stimulated genes (ISGs) and inflammatory cytokines [14]. These host responses prevent viral spread and promote the onset of the adaptive immune response. We present examples of these fascinating, newly-discovered regulatory pathways of viral infection and/or host responses occurring for a broad array of diverse and genetically distant viruses

Transmission of Replicating Viral Genomes by Exosomal Transfer

Common Features of pDC Activation

Virally-Derived MicroRNAs

Conclusions and Perspectives