Anti-viral drug development has taken a significant step forward with this discovery, which was reported in a paper published on February 15 in the Proceedings of the National Academy of Sciences.
Scientists in the department of microbiology are trying to figure out how some RNA manages to evade degradation in this study. “Now we must determine if there is a way to make this work in our favor. “
Students in Muller’s lab study with Muller how Kaposi sarcoma-associated herpesvirus (KSHV) hides in the human body for years before attempting to control human gene expression to complete the viral invasion. A person’s immune system may be compromised to the point that Kaposi sarcoma cancer lesions appear in the mouth, skin, or other organs during this time period.
Molecular biology, genome-wide sequencing, and post-transcriptional sequencing techniques are all employed to learn more about how human cells and viruses maintain their integrity.
Muller’s favorite phrase is, “Viruses are very smart, that’s what I love to say,” “To avoid detection by the body’s immune system, they employ a variety of tactics, including avoiding causing significant damage for a long period of time.
“However, at some point in the future, they reawaken. A massive RNA degradation event is triggered by the virus, which eliminates mRNA from the cell. As a result, the human body is unable to produce the proteins it needs, which opens up a wealth of resources for the virus.
Muller’s team, including lead author and graduate student Daniel Macveigh-Fierro and co-authors and undergraduates Angelina Cicerchia, Ashley Cadorette, and Vasudha Sharma, has been investigating how and why some RNA are able to evade viral degradation.
An “We show that RNA that escape have a chemical tag on them — a post-transcriptional modification — that makes them different from the others,” is what distinguishes the RNAs that escape, according to Muller’s explanations. “They are able to recruit proteins that protect them from degradation by having this tag, M6A, on them.”
KSHV has been Muller’s focus since she was an undergraduate student in her native France.
In order to protect the RNA from degradation, “We know you need this protein to protect the RNA from degradation, but we still don’t know how that physically stops the degradation, so that’s what we’re going to look at now,” she says.
An understanding of how KSHV infection occurs may lead to the development of RNA therapeutics for viral diseases.
We can use these findings to design better anti-viral drugs and change the course of infection by identifying the determinants of what makes an mRNA resistant or susceptible to viral decay,” Muller says.
