The West Nile and Zika viruses are responsible for healthcare emergencies around the world, affecting hundreds of people. Currently, however, there are no antiviral treatments that specifically target these viruses. Can the findings from a new mouse study turn the table on West Nile and Zika?

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A new finding from a study in mice may lead to a targeted treatment for the West Nile and Zika viruses.

Over the past few years, researchers and medical professionals far and wide have joined forces to confront several viral outbreaks.

Two of the most concerning outbreaks have been of the West Nile and Zika viruses.

The West Nile virus is carried by mosquitoes, and it originally affected only regions in temperate and tropical regions.

However, since it entered the United States in 1999, it has been a constant presence in the country. Rates of infection have been on the rise this past year, with 834 cases across 47 states and the District of Columbia having been reported to the Centers for Disease Control and Prevention (CDC).

Of these, 65% were severe, leading to neuroinvasive conditions such as meningitis and encephalitis.

As yet, there have been no outbreaks of the Zika virus — which is also carried by mosquitoes — in the U.S. However, there were many cases of this virus carried by people who had traveled to affected areas, such as Brazil.

The most cases of “imported” Zika virus in the U.S. occurred in 2015 and 2016, when the Zika outbreak peaked in South America.

Although the Zika virus does not usually produce any concerning symptoms in adults, if it infects a pregnant woman, it can cause microcephaly in the fetus.

Despite the potential dangers that accompany these viruses, there are currently no antiviral treatments that specifically target either of them. Doctors usually focus on symptom management.

Now, however, the findings of a recent study in mice may finally lead to a targeted treatment for both Zika and the West Nile virus.

A team from Georgia State University in Atlanta conducted this research, the results of which feature in the journal Frontiers in Microbiology. It used mice to find out what biological mechanisms might lead the way to an effective therapy against flaviviruses such as Zika and West Nile.

The investigators focused on the Z-DNA binding protein 1 (ZBP1), which is involved in triggering the immune response against viruses.

They observed that in mice infected with either the West Nile virus or Zika, ZBP1 appeared to restrict virus replication, thereby barring it from spreading. It also seemed to prevent mice infected with more severe forms of the West Nile virus from developing encephalitis.

However, they also saw that in mice engineered not to produce ZBP1, strains of West Nile virus that did not infect the brain led to mortality in every single case.

“It’s significant,” says senior study author Mukesh Kumar, “because you take a virus that has never been shown to kill anything and if you block this protein the virus will just kill everything.”

“We discovered that when cells are infected with viruses such as Zika and West Nile, they respond by triggering necroptosis, a form of programmed cell death, via ZBP1 signaling,” he adds.

“This inhibits viral replication and spread, allowing the immune system to clear the virus,” notes Kumar.

Following on from these results, the researchers believe that finding a way of increasing ZBP1 expression might provide an effective weapon against flaviviruses.

Such a treatment would also be able to safely target West Nile once it reaches the nervous system — a feat that current treatments are incapable of.

“If you try to open barriers to the brain, you may be making it worse,” says Kumar. “That’s why we try to modulate some part of the host immune response.”

Manipulating a host protein already inside the genome to trigger the body’s natural immune response is a better way of fighting viruses already in the brain.”

Mukesh Kumar