December 23, 2020Miriam Bergeret, MSc
In a recent study published in Nature, researchers have identified the gene responsible for a defense mechanism used by human cells to destroy viral intruders. The process—a specialized type of autophagy, which literally means “self-eating”—could be manipulated to improve human viral defenses.
Essential to normal cell functioning, autophagy is used by cells to isolate and degrade old or unused materials within their cell bodies such as proteins and organelles—their own form of recycling—as well as unwanted bacterial or viral intruders.
What has been less certain, according to Dr. Xiaonan Dong, the lead author of the study and assistant professor of internal medicine at the University of Texas Southwestern (UTSW), is whether there exists a viral-specific autophagy pathway.
To identify genes involved in viral autophagy, Dong and his team used small interfering RNAs (siRNA) to knockdown or silence a panel of over 18,000 different genes in human cells infected with herpes simplex virus type 1 (HSV-1) or Sindbis virus, which causes sindbis fever. For 216 individual genes, silencing their expression led to reduced autophagy of the infecting viruses, suggesting those genes could have a role in the process.
The researchers then narrowed down the results using bioinformatics to analyze the biological processes involved, focusing in on the sorting nexin 5 (SNX5) gene. By deleting the SNX5 gene from human cells infected with different viruses, which prevented viral-specific autophagy, then restoring it by reintroducing the gene, the researchers demonstrated that SNX5 is required for viral-specific autophagy in response to many different types of viruses, including Zika, West Nile, chikungunya, poliovirus, Coxsackievirus B3, and influenza A.
Moreover, when SNX5 was silenced, the researchers did not observe any changes to other autophagic processes used for cell recycling or “eating” bacteria, suggesting that SNX5 is specific to virus-induced autophagy. The finding could lead to new ways of fighting viral infections.
"By learning how cells naturally take up and degrade viruses," Dong said in a recent press release, "we could discover ways to augment this process, creating a more general strategy for developing broad-spectrum antiviral therapeutics that combat an array of different viral infections."