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Journal Club: Mutation helps Zika virus evolve to more easily infect mosquitoes, spread infection

A newly discovered mutation makes it easier for the Zika virus to infect Aedes aegypti mosquitos, a common Zika carrier.   Image: James Gathany.

A newly discovered mutation makes it easier for the Zika virus to infect Aedes aegypti mosquitos, a common Zika carrier.
Image: James Gathany

Scientists discovered the Zika virus over half a century ago. But it wasn’t until recent outbreaks in French Polynesia and South America that the mosquito-borne virus, now associated with Guillain-Barre syndrome in adults and microcephaly in newborn babies, reached epidemic levels. “We are very curious about why the virus became explosive only during the past few years,” says virologist Pei-Yong Shi of the University of Texas Medical Branch.

Now, he and colleagues have uncovered one possible explanation—a new mutation that makes it easier for the virus to infect mosquitoes. They recently reported their findings in Nature.

Shi and his team first tested whether a recent strain of Zika could infect mosquitoes more easily than a strain scientists had isolated before the epidemics. They exposed uninfected Aedes aegypti mosquitoes, a common Zika carrier, to two groups of mice, one carrying the recent strain, the other the pre-epidemic one. They found that mosquitoes that fed on mice carrying the pre-epidemic strain were infected in fewer numbers.

The team examined the blood of the two mouse groups and found that the more recent virus released much higher levels of a protein known as NS1, which has been shown to help other related viruses overcome mosquito immune defenses.

By comparing genetic differences between a pre- and a post-epidemic Zika strain, they discovered that the post-epidemic strain’s ability to secrete more NS1 was caused by a mutation in the chain of amino acids that make up the protein. They then looked for the mutation in over 30 strains of the virus. Although missing in the four pre-epidemic strains, the mutation was present in every strain collected after the French Polynesia outbreak in 2013.

In a final experiment, the researchers followed Zika strains through the entire transmission cycle from mosquito to mammal and back to mosquito. They began with mosquitoes that were infected with either a post-epidemic strain, a pre-epidemic strain, or the pre-epidemic strain engineered to have the NS1 mutation. The two strains carrying the mutation caused higher NS1 levels in the mice and ultimately higher levels of infection in mosquitoes that later fed on those mice.

“This is the first demonstration that a mutation can enhance the mosquito infection,” says Shi. “But we believe there is more than one change in the viral genome of Zika that caused this explosive epidemic.” He is now searching for other mutations that might also ramp up transmission from mammals to mosquitoes, as well as mutations that could enhance transmission from mosquitoes back to mammals.

“It’s important to understand viral evolution,” says Mark Challberg, a program officer in the virology branch of the National Institute of Allergy and Infectious Diseases, which helped fund the study. “There are so many ways viruses have of becoming better pathogens.”

“Since it is such a specific mutation, the next step is to look at how it changes the protein structure or function to make the virus more pathogenic,” says maternal-fetal medicine specialist and Zika evolution researcher Stephanie Valderramos of the University of California, San Francisco Medical Center, who was not involved in the study.

Challberg, Valderramos, and Shi agree that the paper’s findings aren’t likely to lead to a strategy for stopping the spread of Zika in the near future. But as researchers learn more about how the mutation actually changes the function of the protein, Challberg notes, researchers might begin to look for it in other related viruses that haven’t yet reached epidemic levels. If it functions similarly in those viruses, its presence could tip scientists off that another epidemic may be imminent.

 

 

 

 

 

 

 

Categories: Biochemistry | Immunology | Infectious disease | Journal Club | Medical Sciences and tagged | | | |
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One Response to Journal Club: Mutation helps Zika virus evolve to more easily infect mosquitoes, spread infection

  1. The mechanisms of circumventing the immune response need to be evaluated. Perhaps investigating the role of long non coding RNAs.

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