Good news! Advances in virology are pouring forth! We are beating the pathogens one step at a time!
The approach applied here may significantly expedite future research!
"A mitochondrial gene plays a crucial role in genetic susceptibility to Zika, dengue and SARS-CoV-2 infections, according to a new study...
The study ... provides proof of principle that cell-based genome-wide association studies (GWAS) could be a valuable tool for studying genetic susceptibility to infections and other diseases. Genome-wide association studies scan the genomes of hundreds or thousands of people looking for genetic changes associated with diseases. ...
built a laboratory platform that is essentially a GWAS study in a dish. Instead of enrolling people, they used cells donated by patients that were coaxed back into a stem-cell like or early developmental state that can grow into any other type of tissue with the appropriate growth factor. Then, they used the platform to screen for genes that increase the likelihood of infection with Zika virus. ...
Over the past decade and a half, GWAS studies have emerged as a powerful tool to study genetic risk factors for disease ...
used CRISPR gene-editing technology to remove the NDUFA4 gene in the cells. He found that the cells lacking this gene are less susceptible to infection with Zika, the dengue virus and the SARS-CoV-2 virus. By contrast, cells from patients with COVID-19 expressed higher levels of NDUFA4 than cells from healthy donors. ... showed that the loss or reduced expression of the NDUFA4 gene stresses the mitochondria, causing mitochondrial proteins to leak into the cell’s cytoplasm and triggers an innate immune response usually reserved to fight infection. ..."
built a laboratory platform that is essentially a GWAS study in a dish. Instead of enrolling people, they used cells donated by patients that were coaxed back into a stem-cell like or early developmental state that can grow into any other type of tissue with the appropriate growth factor. Then, they used the platform to screen for genes that increase the likelihood of infection with Zika virus. ...
Over the past decade and a half, GWAS studies have emerged as a powerful tool to study genetic risk factors for disease ...
used CRISPR gene-editing technology to remove the NDUFA4 gene in the cells. He found that the cells lacking this gene are less susceptible to infection with Zika, the dengue virus and the SARS-CoV-2 virus. By contrast, cells from patients with COVID-19 expressed higher levels of NDUFA4 than cells from healthy donors. ... showed that the loss or reduced expression of the NDUFA4 gene stresses the mitochondria, causing mitochondrial proteins to leak into the cell’s cytoplasm and triggers an innate immune response usually reserved to fight infection. ..."
From the abstract:
"Population-based studies to identify disease-associated risk alleles typically require samples from a large number of individuals. Here, we report a human-induced pluripotent stem cell (hiPSC)-based screening strategy to link human genetics with viral infectivity. A genome-wide association study (GWAS) identified a cluster of single-nucleotide polymorphisms (SNPs) in a cis-regulatory region of the NDUFA4 gene, which was associated with susceptibility to Zika virus (ZIKV) infection. Loss of NDUFA4 led to decreased sensitivity to ZIKV, dengue virus, and SARS-CoV-2 infection. Isogenic hiPSC lines carrying non-risk alleles of SNPs or deletion of the cis-regulatory region lower sensitivity to viral infection. Mechanistic studies indicated that loss/reduction of NDUFA4 causes mitochondrial stress, which leads to the leakage of mtDNA and thereby upregulation of type I interferon signaling. This study provides proof-of-principle for the application of iPSC arrays in GWAS and identifies NDUFA4 as a previously unknown susceptibility locus for viral infection."
A human iPSC-array-based GWAS identifies a virus susceptibility locus in the NDUFA4 gene and functional variants (open access)
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