Health A Scarier Zika

A sin­gle mu­ta­tion may make the virus more devastating to new­borns

Newsweek International - - NEWSWEEK - BY KATE SHERIDAN @sheri­dan_kate

seen among chil­dren in­fected with the Zika virus have haunted many of the peo­ple who live in re­gions where mos­qui­toes carry the pathogen, in­clud­ing the U.S., South Amer­ica, Africa and South­east Asia. It turns out that a sin­gle ge­netic change in the virus may be re­spon­si­ble.

The de­fect, known as mi­cro­cephaly, wreaks all kinds of phys­i­cal and de­vel­op­men­tal havoc. Chil­dren with mi­cro­cephaly may have seizures, hear­ing loss, dif­fi­culty see­ing or mov­ing, and may not learn to sit, stand or walk at the same rate as other chil­dren. They may also have in­tel­lec­tual dis­abil­i­ties. At least 3,000 chil­dren around the world have been born with mi­cro­cephaly or an­other Zika-re­lated brain birth de­fect.

Mi­cro­cephaly was

not al­ways a com­mon birth de­fect in chil­dren af­fected by Zika, and the prob­lem may have gone un­no­ticed dur­ing ear­lier out­breaks be­cause fewer in­fected women were preg­nant. But as the epi­demic changed—ex­pand­ing in Brazil, most no­tably—the prob­lem be­came more no­tice­able, says Dr. Michael Di­a­mond, an in­fec­tious dis­eases spe­cial­ist at the Washington Univer­sity School of Medicine in St. Louis.

“[Zika] will come back at some point,” says Di­a­mond. “I can’t tell you when, but it will come back at some point. And if it comes back, are we going to be in the same place that we were last time—with noth­ing—or are we going to con­tinue to study it, un­der­stand­ing it might come back worse than it is now?”

A group of Chi­nese re­searchers led by Cheng-feng Qin, a vi­rol­o­gist at the Bei­jing In­sti­tute of Mi­cro­bi­ol­ogy and Epi­demi­ol­ogy, won­dered if the virus had mu­tated, be­com­ing more vir­u­lent and dam­ag­ing to the de­vel­op­ing hu­man brain. To test this the­ory, he sep­a­rated new­born mice into four groups and in­jected one of four dif­fer­ent strains of the virus into their brains. One strain was as­so­ci­ated with a 2010 out­break; three strains were iso­lated dur­ing the out­break from 2015 to 2016. He also tested the virus on hu­man brain stem cells.

Mice in­fected with one par­tic­u­lar strain, called VEN/2016, de­vel­oped brains that were far smaller than those of mice in­fected with other strains. Their brains were also

“[Zika] will come back at some point. I can’t tell you when, but it will come back.”

smaller after be­ing in­fected with a virus cre­ated to carry just one of the newer mu­ta­tions found in VEN/2016. That mu­ta­tion changed one com­po­nent of a pro­tein called prm.

The sin­gle ge­netic ab­nor­mal­ity al­ters the course of the dis­ease. “This spe­cific mu­ta­tion can in­deed make the virus more ag­gres­sive,” says Alysson Muotri, who re­searches the Zika virus at the Univer­sity of Cal­i­for­nia, San Diego, but was not in­volved in the new pa­per.

The break­through, pub­lished last month in Sci­ence, could be cru­cial for the treat­ment of fu­ture out­breaks. Al­though con­cerns over Zika have di­min­ished since last year, the prob­lem has not dis­ap­peared. With so many ar­eas in North Amer­ica now cov­ered in stag­nant flood­wa­ters, ques­tions linger about what im­pact re­cent storms could have on the trans­mis­sion of the virus. The new find­ing is a first step to­ward know­ing how and why the Zika virus causes birth de­fects—and which forms of the virus might be par­tic­u­larly dan­ger­ous.

Al­though the re­sults of Qin’s re­search were strong, the method­ol­ogy left many re­searchers with ques­tions. In­ject­ing the virus straight into a mouse’s brain is not the usual path the virus takes to a de­vel­op­ing fe­tus. In most cases, a mos­quito bites a preg­nant woman, then the virus spreads through her body and crosses the pla­centa to reach the womb. “[In­ject­ing it] inside the brain, it works. The ques­tion is, Does it work out­side the brain?” says Jean Pierre Schatz­mann Peron, an

im­mu­nol­o­gist at the Univer­sity of São Paulo in Brazil.

The an­swer may be no. The mu­tated pro­tein iden­ti­fied in Qin’s study is found on the sur­face of the virus. That might make it more “vis­i­ble” to the mother’s im­mune sys­tem, en­abling the body to at­tack the in­vader be­fore it reaches the fe­tus.

Ex­actly why this mu­ta­tion makes the virus work dif­fer­ently is un­clear, says Schatz­mann Peron, and it may not be the sole per­pe­tra­tor. The more ag­gres­sive Zika virus could be ex­ac­er­bated by other is­sues that make an in­fant even more sus­cep­ti­ble to mi­cro­cephaly.

“This [mu­ta­tion] can change the bi­ol­ogy of the virus, but it doesn’t fully ex­plain what’s going on,” says Muotri. En­vi­ron­men­tal fac­tors, the per­son’s ge­netic back­ground and pre­vi­ous ex­po­sure to other viruses or vac­cines could all be in­volved. “It’s not only about the vi­ral ge­net­ics,” says Muotri. “There are prob­a­bly other fac­tors that play a role.”

Qin and his team are now search­ing for those fac­tors, but Di­a­mond says other ap­proaches are also needed. Ideally, he says, sci­en­tists would use sim­i­lar ex­per­i­ments with mon­keys or chim­panzees, al­low­ing the virus with this mu­ta­tion to in­fect the an­i­mals from mos­qui­tos and then watch­ing how it af­fects fe­tal devel­op­ment.

Though the mos­quito that spreads Zika can be found in sev­eral Euro­pean coun­tries, ac­cord­ing to the World Health Or­ga­ni­za­tion, the risk for peo­ple who don’t travel out­side of Europe has stayed rel­a­tively low. Just over 2,000 cases of Zika were re­ported across Europe in 2016, nearly all of which were as­so­ci­ated with re­cent travel.

But as Di­a­mond points out, the virus could re-emerge any­time, and we need to be pre­pared.

BABY STEPS Cheng-feng Qin, right, led, a group of Chi­nese re­searchers who found ev­i­dence that, at one point, the Zika virus be­came more ag­gres­sive.

OUT­BREAK With so many ar­eas in North Amer­ica now cov­ered in stag­nant flood­wa­ters, ques­tions linger about what im­pact re­cent storms could have on the mos­quito-borne virus.

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