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Michigan researchers find new clues to unlocking Zika virus

Jul 27, 2016

Scientists have unlocked new information about the Zika virus that could eventually contribute to a possible cure – and in the shorter term, may help create faster, simpler tests for identifying if someone’s been infected with the virus.

That’s especially important with Zika, because the virus itself is thought to leave the body pretty fast; maybe after about a week, says Janet Smith, Director of the Center for Structural Biology at the University of Michigan Life Sciences Institute and a professor of biological chemistry.

“In a typical Zika infection, you clear the infection, it’s like, not as bad as a cold,” she says. “It’s just gone, you don’t even know you had it.”

But especially for pregnant women, figuring out if they’ve been infected with Zika in the past – particularly during their pregnancy – is critical.

The top model is Zika, and the bottom is Dengue. Super similar, but crucially different.
Credit "Extended surface for membrane association in Zika virus NS1 structure"

The problem is, at the molecular level, Zika looks a lot like other similar viruses, like West Nile and Dengue fever.

That makes testing trickier.

“So you want to develop a test that’s only going to give you a positive if they had Zika. If you are pregnant, you need a very reliable answer,” Smith says. “Because you're going to have to make some decisions. And you need a good answer."

Finding Zika's teeny tiny fingerprints 

To be clear: Smith’s not saying that anybody’s giving pregnant women false positives for Zika. The CDC and the state's labs have significant testing protocols already in place, and the Michigan Department of Health and Human Services describes its testing as “state of the art.”

But what Smith and her team – which includes researchers at Purdue University and the Argonne National Laboratory – have been able to do is identify and map out the teeny, tiny fingerprints that only a Zika molecule has.

The scientific term for that? Mapping the Zika virus’s protein structure.

Researchers are hoping doctors will be able to take Zika’s molecular fingerprint – a little bit of its unique protein structure – and expose it to a person’s white blood cells in a simple lab test.

If the blood cells recognize the Zika protein and attack it, that’s a clear positive that the person has been infected with Zika, and not West Nile or Dengue, according to Smith.

“So what we’re doing is taking some blood and saying: ‘Ok, with the cells that are in this person’s blood – if we give them a stimulus with Zika, are they gonna react?’” Smith says. “If they react immediately, it’s because they’ve already seen it. It’s the memory of the immune system.”

More than just testing, though, Smith hopes that understanding what makes the Zika virus unique will eventually help researchers get a better sense of how it affects the human body.

Viruses, she says, are incredibly adept at figuring out how to use our own immune systems against us – and the more we can unlock a virus’ secrets, the better we’ll be able to treat it.

Using laser beams "one-tenth the diameter of a human hair"

In a “science is really cool” note, the lab where researchers x-rayed this tiny Zika protein structure is the size of a baseball stadium. It’s in a giant, round warehouse in Illinois called the Argonne National Laboratory.  

What Smith’s team x-rayed was a tiny crystal “about one-tenth the diameter of a human hair” that contained the Zika protein.

Argonne National Lab outside Chicago
Credit www.anl.gov

“And then we hit them with a beam of x-rays, which is of similar size to the crystal … and our little place where we put the sample, is about 70 meters – so about two-thirds of a football field – away from where [they] generate the x-rays.

“And we have to hit this thing that’s about a tenth of a hair, with a beam that’s a tenth of a hair. And the sample has to be held still, no vibrations.

“So the analogy that I made … was that that’s the equivalent of taking a laser pointer, and hitting a pumpkin in Juneau, Alaska while you’re sitting in Washington D.C.”

Their findings were published this week in the journal Nature Structural & Molecular Biology.

Quick update: Yesterday we reached out to the CDC and the Michigan Department of Health and Human Services about what testing for Zika looks like right now. Today, MDHHS sent us some more info, and we're including that below. 

"For testing performed by MDHHS, first patients must meet the criteria for testing.  This information is on the www.michigan.gov/zikawebsite, under the tab “Zika Virus Information for Healthcare Providers”.  We request both serum and urine on most patients who meet the criteria for Zika testing.  Our lab has a suite of tests that may be performed, based on a number of factors, including when the sample was collected in relation to a patient’s illness onset or potential exposure to Zika virus.  The lab has just updated the details of the tests that will be performed on samples from a patient meeting our criteria for testing, and they can be found athttp://www.michigan.gov/mdhhs/0,5885,7-339-71551_2945_5103-215861--,00.html.

"There is a commercial test currently available for Zika virus.  It is a PCR methodology performed on blood.  Because there is a pretty narrow window for detecting Zika virus in the blood of many patients, that test is of limited usefulness.  Patients with a negative PCR test may need to be tested further with serologic methods that look for antibodies to the virus.  There is currently no commercial test available that detects antibodies to Zika virus.  The other issue with antibody testing is that it is less specific than finding the virus in a sample, and viruses other than Zika can produce a positive result on the Zika antibody test.  At this time, only testing provided by state and federal public health laboratories is sophisticated enough to potentially confirm a Zika virus infection through antibody detection."