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06.19.2017

Study ID’s potential new target to treat viral infections

Manipulating protein leads to better awareness of processes involved in viral replication

By Michael McCarthy  |  HSNewsBeat  |  Updated 1:15 PM, 06.19.2017

Posted in: Research

  • Dr. Susan Fink, a lab medicine specialist, displays containers used in a test of viral infection. Michael McCarthy

Research has identified a new way that viruses keep infected cells alive – so the viruses can use the cells to reproduce. The finding suggests it may be possible to target this process to treat viral infections.

The lead researcher was Dr. Susan Fink, assistant professor of laboratory medicine at the University of Washington School of Medicine. She worked with colleagues at Yale University and Kanazawa Medical University in Japan.

The investigators were examining a process called the unfolded-protein response. It involves a cellular structure called the endoplasmic reticulum, where newly made proteins are folded and modified before being released into the cell. The response occurs when the endoplasmic reticulum becomes overloaded with unfolded proteins, which can occur in a number of situations, including viral infection.

The researchers suspected that two proteins activated in the unfolded-protein response, X-box binding protein 1 (XBP1) and inositol-requiring enzyme 1-alpha (IRE1-alpha), helped fight viral infection by promoting the production of infection-fighting proteins called interferons. To test their hypothesis, they used cells that did not have the genes for making the XBP1 to see if it made the cells more susceptible to infection.

They found that these cells were indeed more susceptible – but not because the cells had an impaired interferon response. Instead they found that removing XBP1 had disabled apoptosis, a “self-destruct” strategy in which an infected cell sacrifices itself to keep a virus from spreading.

Further study revealed that the lack of XBP1 activated the other protein they were studying, IRE1-alpha, which when activated acted on other factors that blocked apoptosis.

To see what role this blockade might play in patients with viral infections, the researchers looked at cells infected by hepatitis C. They demonstrated that the virus encodes a protein that also activates IRE1-alpha, promoting the survival of infected cells and viral replication.

“The finding suggests that drugs that target this effect of activated IRE1-alpha could be effective against hepatitis C and other viral infections,” Fink said.

Tagged with: virus, proteins, cell biology
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