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Confocal Imaging of Double-Stranded RNA and Pattern Recognition Receptors in Negative-Sense RNA Virus Infection
Published on: January 26, 2019
Interaction of the innate immune system with positive-strand RNA virus replication organelles
Enzo Maxim Scutigliani1, Marjolein Kikkert1
1Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract:
The potential health risks associated with (re-)emerging positive-strand RNA (+RNA) viruses emphasizes the need for understanding host-pathogen interactions for these viruses. The innate immune system forms the first line of defense against pathogenic organisms like these and is responsible for detecting pathogen-associated molecular patterns (PAMPs). Viral RNA is a potent inducer of antiviral innate immune signaling, provoking an antiviral state by directing expression of interferons (IFNs) and pro-inflammatory cytokines. However, +RNA viruses developed various methods to avoid detection and downstream signaling, including isolation of viral RNA replication in membranous viral replication organelles (ROs). These structures therefore play a central role in infection, and consequently, loss of RO integrity might simultaneously result in impaired viral replication and enhanced antiviral signaling. This review summarizes the first indications that the innate immune system indeed has tools to disrupt viral ROs and other non- or aberrant-self membrane structures, and may do this by marking these membranes with proteins such as microtubule-associated protein 1A/1B-light chain 3 (LC3) and ubiquitin, resulting in the recruitment of IFN-inducible GTPases. Further studies should evaluate whether this process forms a general effector mechanism in +RNA virus infection, thereby creating the opportunity for development of novel antiviral therapies.
Insights
The innate immune system can disrupt viral replication by targeting viral replication organelles (ROs). This host-pathogen interaction, involving proteins like LC3 and ubiquitin, offers potential for new antiviral therapies against positive-strand RNA viruses.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Positive-strand RNA (+RNA) viruses pose health risks, necessitating understanding of host-pathogen interactions.
- The innate immune system detects pathogen-associated molecular patterns (PAMPs), including viral RNA, to initiate antiviral responses.
- Viruses evade immune detection by sequestering RNA replication within viral replication organelles (ROs).
Purpose of the Study:
- To review evidence suggesting the innate immune system can disrupt viral replication organelles (ROs).
- To explore mechanisms by which host factors target aberrant membrane structures during viral infection.
- To identify potential therapeutic targets for antiviral strategies.
Main Methods:
- Literature review of studies on host-pathogen interactions and innate immunity.
- Analysis of mechanisms involving protein tagging (e.g., LC3, ubiquitin) of viral structures.
- Examination of the role of IFN-inducible GTPases in antiviral defense.
Main Results:
- Viral replication organelles (ROs) are crucial for +RNA virus infection.
- Disruption of RO integrity can impair viral replication and enhance antiviral signaling.
- The innate immune system employs proteins like LC3 and ubiquitin to target viral ROs, recruiting IFN-inducible GTPases.
Conclusions:
- The innate immune system possesses mechanisms to disrupt viral replication organelles.
- Targeting viral ROs represents a potential strategy for developing novel antiviral therapies.
- Further research is needed to confirm this as a general antiviral mechanism against +RNA viruses.
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