A Novel Mechanism Underlying the Innate Immune Response Induction upon Viral-Dependent Replication of Host Cell mRNA: A Mistake of +sRNA Viruses' Replicases

Abstract

Viruses are lifeless particles designed for setting virus-host interactome assuring a new generation of virions for dissemination. This interactome generates a pressure on host organisms evolving mechanisms to neutralize viral infection, which places the pressure back onto virus, a process known as virus-host cell co-evolution. Positive-single stranded RNA (+sRNA) viruses are an important group of viral agents illustrating this interesting phenomenon. During replication, their genomic +sRNA is employed as template for translation of viral proteins; among them the RNA-dependent RNA polymerase (RdRp) is responsible of viral genome replication originating double-strand RNA molecules (dsRNA) as intermediates, which accumulate representing a potent threat for cellular dsRNA receptors to initiate an antiviral response. A common feature shared by these viruses is their ability to rearrange cellular membranes to serve as platforms for genome replication and assembly of new virions, supporting replication efficiency increase by concentrating critical factors and protecting the viral genome from host anti-viral systems. This review summarizes current knowledge regarding cellular dsRNA receptors and describes prototype viruses developing replication niches inside rearranged membranes. However, for several viral agents it's been observed both, a complex rearrangement of cellular membranes and a strong innate immune antiviral response induction. So, we have included recent data explaining the mechanism by, even though viruses have evolved elegant hideouts, host cells are still able to develop dsRNA receptors-dependent antiviral response.

The Dietary Intake of Carrot-Derived Rhamnogalacturonan-I Accelerates and Augments the Innate Immune and Anti-Viral Interferon Response to Rhinovirus Infection and Reduces Duration and Severity of Symptoms in Humans in a Randomized Trial

“…Most ARI resolve within one to two weeks and the host response is driven to a large extent by the innate immune system. Innate immune responses are triggered by signaling via pattern-recognition receptors (PRR) such as Toll-like receptors (TLR), double-strand RNA-activated protein kinase R (PKR) and retinoic acid-inducible gene-I (RIG-I)-like receptors that sense pathogen-associated molecular patterns (PAMPs) [6,7]. PRR funnel their signals into interactions with regulated signaling cascades, which then initiate the key antiviral interferon response as well as other common anti-viral and innate immune responses [8,9].…”

Characterization of Mayaro virus (strain BeAn343102) biology in vertebrate and invertebrate cellular backgrounds

“…Double labelling of organelle and viral nonstructural proteins showed that CPV-I are derivatives of late endosomes and lysosomes, while monensin treatment results in accumulation of E1/E2 glycoproteins of SFV in the trans-Golgi network (TGN), indicating the TGN origin of CPV-II [43,44]. The replication complexes are strategically concentrated in CPV-I and replication spherules for efficient viral genome replication and to escape the cellular antiviral response [45]. These replication spherules that have access to the host cellular raw materials through an opening toward the cytoplasm were seen either inside CPV-I or transported to the plasma membrane [42,46].…”

Everything you wanted to know about Mayaro virus but were afraid to ask: Characterization and lifecycle of Mayaro virus in vertebrate and invertebrate cellular backgrounds

“…Double labeling of organelle and viral nonstructural proteins showed that CPV-I are derivatives of late endosomes and lysosomes, while monensin treatment results in accumulation of E1/E2 glycoproteins of SFV in the trans-Golgi network (TGN), indicating TGN origin of CPV-II 26,27 . The replication complexes are strategically concentrated in CPV-I and replication spherule for efficient viral genome replication and to escape the cellular antiviral response 28 . These replication spherules that has access to the host cellular raw materials through an opening toward the cytoplasm were seen either inside CPV-I or transported to the plasma membrane 29 Most commonly blebs are seen during apoptosis and contains part of the cytoplasm (~2%) with or without organellar fragments for recycling by the phagocytic cells 35,36 .…”