Chikungunya Replication Protein Identified
This research opens up therapeutic avenues in the fight against the deadly chikungunya virus.
The name Chikungunya derives from a word in the Kimakonde language, meaning “to become contorted.” It is aptly named so because the severe muscle and joint pains endured by the patients prevent them from moving frequently or performing their daily activities.
Chikungunya is an infectious disease caused by a mosquito-borne virus transmitted to humans. It is characterized by high fever including intense joint and muscle pain.
The mechanisms of infection of human cells with the virus remain very poorly understood. Scientists have now identified a protein that is crucial for the virus to replicate within its target cells.
Chikungunya Replication Protein Identified- The Challenges
The clinical manifestations of the disease are well understood though the mechanisms by which the virus infects human cells and multiplies remain poorly elucidated.
None of the previous studies had succeeded in explaining why the virus preferentially targets the muscle and joint cells, consequently leading these clinical signs.
Dr. Ali Amara led the research at the AP-HP Saint-Louis Hospital Research Institute in Paris. It was a collaborative study with Marc Lecuit’s team from Institut Pasteur, Inserm, and Universit
é de Paris.Researches have identified that the FHL1 protein is a critical cellular factor for the replication and pathogenesis of chikungunya.
FHL1 is a molecule present mainly in the muscle cells and fibroblasts. These cells are the preferred targets of the Chikungunya virus. FHL1 plays an essential role in healthy muscle physiology. It is now thought to be diverted from that function by the virus to ensure its replication in the target cells.
Chikungunya Replication Protein Identified- The Study Methodology
Dr. Amara’s team used the CRISPR-Cas9 technology to systematically screen the genome of human cells to identify the host factors necessary for viral replication.
Subsequently, they isolated the gene coding for the FHL1 protein. The team of researchers then conducted a series of experiments showing the incapacity of the virus to infect cells whose FHL1 expression had been abolished.
Additionally, the scientists have shown that the virus was incapable of multiplying within cells derived from patients suffering Emery-Dreifuss muscular dystrophy. It is a rare genetic disease.
This disease is the result of mutations of the FHL1 gene responsible for the breakdown of the FHL1 protein. The researchers have demonstrated that the cells of these patients are resistant to the virus.
Finally, the scientists performed in vivo experiments in mice whose Fhl1 gene was invalidated. They have shown that these animals are resistant to infection and do not develop the disease, whereas the virus multiplies and causes significant muscle lesions in mice expressing a functional FHL1 protein.
These observations demonstrate that the FHL1 protein plays a crucial role in chikungunya virus replication and pathogenesis.
Chikungunya Replication Protein Identified- The FHL1 Protein
The precise role played by FHL1 in the viral infection is not fully understood. The scientists have discovered that FHL1 interacts with a viral protein known as nsP3. It is binding to this that FHL1 protein participates in the replication of the virus.
The team of scientists will now look into the mechanism of action at the molecular level in and discover the reason behind FHL1’s specificity to the chikungunya virus.
Elucidating the molecular structure of the FHL1-nsP3 complex could be a significant step forward in the development of antivirals that block the replication of the virus.
Currently, only symptomatic treatments are available for patients infected with chikungunya.
