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Mechanisms of Non-segmented Negative Sense RNA Viral Antagonism of Host RIG-I-Like Receptors.

ABSTRACT: The pattern recognition receptors RIG-I-like receptors (RLRs) are critical molecules for cytosolic viral recognition and for subsequent activation of type I interferon production. The interferon signaling pathway plays a key role in viral detection and generating antiviral responses. Among the many pathogens, the non-segmented negative sense RNA viruses target the RLR pathway using a variety of mechanisms. Here, I review the current state of knowledge on the molecular mechanisms that allow non-segmented negative sense RNA virus recognition and antagonism of RLRs.

SUBMITTER: Leung DW

PROVIDER: S-EPMC6879798 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Mechanisms of Non-segmented Negative Sense RNA Viral Antagonism of Host RIG-I-Like Receptors.

Leung Daisy W DW

Journal of molecular biology 20190614 21

The pattern recognition receptors RIG-I-like receptors (RLRs) are critical molecules for cytosolic viral recognition and for subsequent activation of type I interferon production. The interferon signaling pathway plays a key role in viral detection and generating antiviral responses. Among the many pathogens, the non-segmented negative sense RNA viruses target the RLR pathway using a variety of mechanisms. Here, I review the current state of knowledge on the molecular mechanisms that allow non-s ...[more]

PMID: 31202887

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Project description:Negative-sense RNA viruses (NSVs) rely on prepackaged viral RNA-dependent RNA polymerases (RdRp) to replicate and transcribe their viral genomes. Their replication machinery consists of an RdRp bound to viral RNA which is wound around a nucleoprotein (NP) scaffold, forming a viral ribonucleoprotein complex. NSV NP is known to regulate transcription and replication of genomic RNA; however, its role in maintaining and protecting the viral genetic material is unknown. Here, we exploited host microRNA expression to target NP of influenza A virus and Sendai virus to ascertain how this would impact genomic levels and the host response to infection. We find that in addition to inducing a drastic decrease in genome replication, the antiviral host response in the absence of NP is dramatically enhanced. Additionally, our data show that insufficient levels of NP prevent the replication machinery of these NSVs to process full-length genomes, resulting in aberrant replication products which form pathogen-associated molecular patterns in the process. These dynamics facilitate immune recognition by cellular pattern recognition receptors leading to a strong host antiviral response. Moreover, we observe that the consequences of limiting NP levels are universal among NSVs, including Ebola virus, Lassa virus, and measles virus. Overall, these results provide new insights into viral genome replication of negative-sense RNA viruses and highlight novel avenues for developing effective antiviral strategies, adjuvants, and/or live-attenuated vaccines.IMPORTANCE Negative-sense RNA viruses comprise some of the most important known human pathogens, including influenza A virus, measles virus, and Ebola virus. These viruses possess RNA genomes that are unreadable to the host, as they require specific viral RNA-dependent RNA polymerases in conjunction with other viral proteins, such as nucleoprotein, to be replicated and transcribed. As this process generates a significant amount of pathogen-associated molecular patterns, this phylum of viruses can result in a robust induction of the intrinsic host cellular response. To circumvent these defenses, these viruses form tightly regulated ribonucleoprotein replication complexes in order to protect their genomes from detection and to prevent excessive aberrant replication. Here, we demonstrate the balance that negative-sense RNA viruses must achieve both to replicate efficiently and to avoid induction of the host defenses.

Dataset Information

Mechanisms of Non-segmented Negative Sense RNA Viral Antagonism of Host RIG-I-Like Receptors.

Publications

Mechanisms of Non-segmented Negative Sense RNA Viral Antagonism of Host RIG-I-Like Receptors.

Similar Datasets

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