Genetic Basis of Intraspecific Variation in Caenorhabditis briggsae Susceptibility to Two Intestinal RNA Viruses

核心概念

Caenorhabditis briggsae wild isolates exhibit natural variation in their susceptibility to two intestinal RNA viruses, Santeuil virus (SANTV) and Le Blanc virus (LEBV), with some strains showing specific resistance to one virus. The genetic basis of this variation was mapped to quantitative trait loci on different chromosomes.

摘要

The study investigates the natural variation in infection specificity of the nematode Caenorhabditis briggsae by two intestinal RNA viruses, Santeuil virus (SANTV) and Le Blanc virus (LEBV).
Key highlights:

Many temperate-origin C. briggsae strains are sensitive to both viruses, while many tropical strains are resistant to both.
Some strains, like HK104, exhibit specific resistance to one virus (LEBV) but not the other (SANTV).
The viral sensitivity pattern matches the strains' geographic and genomic relationships.
The sensitive strains mount a seemingly normal small RNA response that is insufficient to suppress viral infection, while the resistant strains show no small RNA response, suggesting an early block in viral entry or replication.
Genetic mapping using recombinant inbred lines identified quantitative trait loci (QTLs) on chromosomes IV and III conferring resistance to SANTV, and a QTL on chromosome II conferring resistance to LEBV.
Further introgression experiments confirmed these QTLs, providing an avenue to study virus entry, replication, and host-virus specificity mechanisms.

統計資料

The viruses shorten the lifespan of C. briggsae JU1264 (logrank test, p=5.44 × 10−9, p=5.21 × 10−10, p=1.08 x 10-7, for mock vs LEBV, SANTV and both, respectively).
Compared to mock infection, the total brood size is smaller for LEBV infection and co-infection (Wilcoxon rank sum test with continuity correction, p=0.04 and p=0.01, respectively).
JU1264 animals show a significant delay in progeny production when infected with either virus (linear model, p=2.2 × 10−16).

引述

"The fast evolution of host-pathogen interactions makes this approach particularly powerful."
"This diversity provides an avenue for studying virus entry, replication, and exit mechanisms, as well as host-virus specificity and the host response to a specific virus infection."

從以下內容提煉的關鍵洞見

Natural variation in infection specificity of Caenorhabditis briggsae isolates by two RNA viruses

by Alkan,C., Br... 於 www.biorxiv.org 02-12-2024

https://www.biorxiv.org/content/10.1101/2024.02.10.579610v1

深入探究

What are the specific molecular mechanisms underlying the early block in viral entry or replication in the resistant C. briggsae strains?

The resistant C. briggsae strains, such as AF16 and HK104, exhibit an early block in viral entry or replication when infected with SANTV or LEBV. This blockage could be due to several specific molecular mechanisms:

Host Cell Receptors: The resistant strains may lack specific cell surface receptors that are necessary for the viruses to enter the host cells. Without binding to these receptors, the viruses cannot successfully enter and infect the cells.

Intracellular Signaling Pathways: The resistant strains may have altered intracellular signaling pathways that are crucial for viral replication. These pathways could be disrupted or inhibited, preventing the viruses from replicating effectively within the host cells.

Immune Response: The resistant strains may have a robust immune response that quickly recognizes and eliminates the viruses upon entry. This response could involve the activation of antiviral genes, production of interferons, or induction of apoptosis in infected cells.

Viral RNA Degradation: The resistant strains may possess enhanced mechanisms for degrading viral RNA, preventing the viruses from establishing a productive infection. This could involve the activation of RNA interference pathways or other RNA degradation mechanisms.

Cellular Defense Mechanisms: The resistant strains may have specific cellular defense mechanisms that target and inhibit viral replication machinery. These mechanisms could interfere with viral genome replication, transcription, or protein synthesis.

Overall, the early block in viral entry or replication in the resistant C. briggsae strains likely involves a combination of these molecular mechanisms, which collectively contribute to the host's ability to resist viral infection.

How do the identified QTLs interact with each other and with other host factors to confer resistance or specificity against the two viruses?

The Quantitative Trait Loci (QTLs) identified on chromosomes IV and III in the C. briggsae strains play a crucial role in conferring resistance or specificity against the SANTV and LEBV viruses. These QTLs interact with each other and with other host factors in the following ways:

Epistasis: The QTLs on chromosomes IV and III may exhibit epistatic interactions, where the effect of one QTL is dependent on the presence of another. This interaction could modulate the overall resistance or specificity of the host against the viruses.

Gene Expression: The QTLs may regulate the expression of specific genes involved in antiviral defense mechanisms. These genes could be part of the host's immune response pathways, RNA interference pathways, or other antiviral mechanisms.

Protein Interactions: Proteins encoded by genes within the QTL regions may interact with viral proteins or host factors essential for viral replication. These interactions could disrupt viral processes and inhibit viral propagation within the host cells.

Genetic Background: The genetic background of the host, including other genetic variants and polymorphisms, may influence the effects of the identified QTLs. Interactions between the QTLs and other genetic factors could modulate the overall resistance phenotype.

Environmental Factors: External factors such as temperature, humidity, and food availability could also influence the effects of the QTLs on viral resistance. The interplay between genetic and environmental factors shapes the host's response to viral infections.

In summary, the identified QTLs on chromosomes IV and III interact with each other, as well as with other host factors, to confer resistance or specificity against the SANTV and LEBV viruses. These complex interactions determine the outcome of the host-virus interaction and contribute to the overall defense mechanisms of the host.

Could the insights from this nematode system be leveraged to understand host-virus interactions in other organisms, including humans?

The insights gained from studying the host-virus interactions in the C. briggsae nematode system have the potential to provide valuable knowledge that can be applied to understanding host-virus interactions in other organisms, including humans. Here are some ways in which these insights could be leveraged:

Evolutionary Conservation: Many fundamental biological processes and immune response mechanisms are evolutionarily conserved across different species. By studying host-virus interactions in C. briggsae, we can gain insights into similar processes in other organisms, including humans.

Genetic Basis of Resistance: Understanding the genetic basis of resistance to specific viruses in C. briggsae can shed light on the genetic factors that influence viral susceptibility or resistance in other organisms. This knowledge can be applied to identify potential therapeutic targets or genetic markers for viral infections in humans.

Mechanistic Studies: The molecular mechanisms underlying viral entry, replication, and host defense identified in C. briggsae can provide a framework for studying similar mechanisms in human cells. This comparative approach can help elucidate common pathways and targets for antiviral interventions.

Drug Development: Insights from studying host-virus interactions in C. briggsae can inform the development of antiviral drugs or therapies for human viral infections. Targeting conserved pathways or host factors identified in nematodes could lead to the discovery of novel antiviral strategies.

Disease Models: Nematode systems like C. briggsae can serve as valuable models for studying viral pathogenesis and host responses in a controlled laboratory setting. Findings from these models can be extrapolated to understand similar processes in more complex organisms, including humans.

Overall, leveraging the insights from the nematode system to study host-virus interactions can provide a foundation for advancing our understanding of viral infections in diverse organisms, offering new perspectives and potential solutions for combating viral diseases in humans.