Flu Takeover: How Influenza A Replicates Inside Human Cells, Spreads Infection

May 8th 2017

Virus hijacks host cells to reproduce inside the nucleus.

Scientists have identified the mechanisms by which influenza A hijacks cellular machinery to replicate and spread infection.

In addition, investigators found a link between congenital defects in the RNA exosome and neurodegeneration that occurs in individuals with this rare mutation.

For the study, investigators examined the cells from patients with an RNA exosome mutation. The findings were published inCell, and allowed investigators to further understand how influenza A hijacks the RNA exosome inside the nucleus.

“This study shows how we can discover genes linked to disease—–in this case, neurodegeneration––by looking at the natural symbiosis between a host and a pathogen,” said senior investigator Ivan Marazzi, PhD.

Influenza A is an RNA virus that reproduces inside the nucleus rather than outside. In part, it is responsible for seasonal flus as well as for pandemics such as H1N1.

“We are all a result of coevolution with viruses, bacteria, and other microbes, but when this process is interrupted, which we call the broken symmetry hypothesis, disease can result,” Dr. Marazzi said.

Neurodegeneration caused by a congenital RNA exosome mutation could offer insight into brain disorders such as Alzheimer’s and Parkinson’s disease, according to the authors.

For influenza A, the absence of RNA exosome activity severely compromises viral infectivity but also manifests in human neurodegeneration. This suggests that viruses target essential proteins in rare diseases to continue to adapt.

The results of the study showed that wheninfluenza Aenters the nucleus, the RNA exosome, which is an essential protein complex that degrades RNA to help regulate gene expression.

Because the pathogen needs extra RNA to begin the replication process, the virus will steal molecules from the hijacked exosome, according to the authors.

“Viruses have a very intelligent way of not messing too much with our own biology,” Dr Marazzi said. “It makes use of our byproducts, so rather than allowing the exosome to chew up and degrade excess RNA, it tags the exosome and steals the RNA it needs before it is destroyed.”

For the virus to grow and spread it requires the presence of an RNA exosome.

“So the agreement between the virus and host is that it is okay for the virus to use some of the host RNA because the host has other ways to suppress the virus that is replicated,” lead author Alex Rialdi, MPH, concluded.

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