Ultrasound could help reduce the use of drugs for patients with rheumatoid arthritis
In the 1970s the researchers had found that certain viruses underwent a RNA modification in order to survive the immune response. This RNA modification is called N6-methyladenosine modification, wrote the researchers. This chemistry has not been clearly understood till now say the researchers and this process became the key to development of the vaccine they said. The RNA modification is a form of “epigenetic methylation”, they wrote.
For testing this theory the team used lab cotton rats to show that the mutated virus lost its virulence and became a vaccine of sorts against HMPV infections. It could help trigger an innate immune response which could fight incoming HMPV infections. Since both HMPV and RSV belong to the same family, this novel vaccine could help fight RSV as well explained the researchers.
The team looked at the effects of RNA modification called the m6A methylation on the HMPV and found that its blockade had an effect on the virulence of the virus. They screened a selection of viruses to isolate the genes that contained the most m6A methylation. To do this they used high-throughput sequencing. In these areas, the team mutated the gene and blocked the RNA modification. Now they studied the effect of the viruses without these modifications. They were introduced into human cells and the viruses stimulated production of a protein called the type I interferon. Interferons are activated when the immune system is activated and these are basically antiviral in nature. Thus, high levels of type 1 interferon meant that the immune system was no activated and capable of fighting the viruses. Li said, “This opened up a big question. Why would a virus lacking this methylation produce a much higher innate immune response?” Looking back at the whole process, the team found out the RNA modification behind the viral survival.
Li explained, “We know that when a virus infects cells, it produces RNA, and human cells in the innate response try to separate self-RNA and nonself-RNA. The virus is smart: It gained this methylation, and now our host innate response is confused. That's how the virus escapes recognition by the innate immune response.” Mijia Lu, the first author of the study, who is also a postdoctoral researcher in Li's laboratory said, “We are very excited about this finding. This novel function of m6A may also be conserved in many viruses.”
As of now the team has filed for a patent to develop this concept for development of a vaccine against HMPV and RSV. Their study was supported by the National Institutes of Health (NIH). Journal reference:
Lu, M., Zhang, Z., Xue, M. et al. N6-methyladenosine modification enables viral RNA to escape recognition by RNA sensor RIG-I. Nat Microbiol (2020). https://doi.org/10.1038/s41564-019-0653-9
Also in Industry News
How to decide whether or not to start treatment for prostate cancer?
Analysis of the SARS-CoV-2 proteome via visual tools
$65m investment increases British Patient Capital’s exposure to life sciences and health technology