Scripps Florida Scientists Find Clue to Why Zika, But Not Its Close Relatives, Causes Birth Defects

15/06/2017

Scripps Florida Scientists Find Clue to Why Zika, But Not Its Close Relatives, Causes Birth Defects JUPITER, FL February 6, 2017 The most frightening aspect of Zika virus has been its ability to produce severe fetal birth defects during pregnancy, especially microcephaly a small head.

Now, scientists from the Florida campus of The Scripps Research Institute (TSRI) have uncovered the details behind the virus's unique ability to cross the placental barrier and expose the fetus to a range of birth defects that often go beyond microcephaly to include eye and joint injury, and even other types of brain damage.

The new study, led by TSRI Associate Professor Hyeryun Choe, was published online ahead of print this week in the journal Proceedings of the National Academy of Sciences.

How Zika virus crosses the placental barrier, while other closely related viruses in the flavivirus family including dengue and West Nile viruses do not, has puzzled researchers since the crisis began some two years ago in Brazil.

Obstacles to reaching the fetal brain are substantial a virus must move from the mother's blood into fetal circulation, which is separated by placental barrier cells designed to prevent that very occurrence.

The researchers found that human umbilical endothelial cells, derived from four donors in the study, proved far more susceptible to Zika infection than to other viruses, with viral counts as much as a hundred or thousand times higher than West Nile or dengue virus. The new research also suggests that Zika virus learned to exploit something of a secret passage, a cell surface molecule known as AXL, while West Nile and dengue viruses did not.

Zika uses AXL to efficiently slip past one of the major barrier cell types in the placenta: fetal endothelial cells, which are the gateway to access fetal circulation, said Choe.

What may help make the Zika virus particularly infectious in cells that other flaviviruses cant infect, said TSRI Research Associate Audrey Richard, a first author of the study, is that it profits from the built-in function of AXL. The physiological function of AXL is to quench activated immune reactions, including the antiviral interferon response, said Richard. By using AXL, Zika virus catches two birds with one stone; it enters cells and also gains favorable environment for its replication inside the cells.

Zika is able to take advantage of AXL by binding to an intermediate molecule known as Gas6, which is present in blood and other bodily fluids. Gas6 acts as an active bridge between the virus and AXL by binding AXL on one end and the virus membrane on the other, helping the virus utilize AXL and gain entry to host cells.

These differences may help explain why, among related viruses, only Zika can efficiently access and infect the fetal bloodstream.

We don't yet understand why Zika virus uses AXL and the others don't, Choe added. The common belief is that all flaviviruses have similar structures, but our findings suggest that Zika virus may have a different average population structure than others. This has significant scientific and clinical implications.

Structural studies show that most of the infectious virion membrane is completely covered with viral proteins, which makes it difficult for Gas6 to bind to the Zika virus membrane underneath the protein shell, said TSRI Research Associate Byoung-Shik Shim, the study's other first author. However, flavivirus particles assume many asymmetric shapes and are in continuous dynamic motion, which likely exposes patches of the virion membrane. Our study suggests that Zika virus exposes enough membrane for Gas6 binding, whereas West Nile and dengue viruses do not.

The researchers also speculated on Zika virus' pathology. AXL is also present in the blood-brain barrier, the eye-blood barrier and the testes where it maintains integrity of the blood vessels and the functions of the testes. It may be used by Zika virus to infect those cells and may explain Zika virus' ability to infect the fetal brain and eye and to transmit sexually.

In addition to Choe, Richard and Shim, other authors of the study, AXL-Dependent Infection of Human Fetal Endothelial Cells Distinguishes Zika Virus from Other Pathogenic Flaviviruses, include Young-Chan Kwon, Yuka Otsuka, Kimberly Schmitt and Fatma Berri of TSRI; Rong Zhang and Michael S. Diamond of Washington University School of Medicine, St. Louis, MO.

The study was supported by start-up funds from the state of Florida, the National Institutes of Health (grants R01 AI110692, R01 AI073755 and R01AI101400).

About The Scripps Research Institute

The Scripps Research Institute (TSRI) is one of the worlds largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs more than 2,500 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists including two Nobel laureates and 20 members of the National Academies of Science, Engineering or Medicine work toward their next discoveries. The institutes graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. In October 2016, TSRI announced a strategic affiliation with the California Institute for Biomedical Research (Calibr), representing a renewed commitment to the discovery and development of new medicines to address unmet medical needs. For more information, see www.scripps.edu.

# # #

For information:

Office of Communicati

LINK:	http://www.scripps.edu/news/press/2017/20170206choe.html...
	See more stories from scripps

Most recent headlines

05/01/2027

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be demoed at CES 2026

Worlds first 802.15.4ab-UWB chip verified by Calterah and Rohde & Schwarz to be ...

01/06/2026

Dolby Sets the New Standard for Premium Entertainment at CES 2026

January 6 2026, 05:30 (PST) Dolby Sets the New Standard for Premium Entertainment at CES 2026 Throughout the week, Dolby brings to life the latest innovatio...

02/05/2026

Dalet Flex LTS Delivers Smarter Search, Faster Editing, and an AI-Ready Foundation for Modern Media

Dalet, a leading technology and service provider for media-rich organizations, t...

01/05/2026

NBCUniversal's Peacock to Be First Streamer to Integrate Dolby's Full Suite of Premium Picture and Sound Innovations

January 5 2026, 18:30 (PST) NBCUniversal's Peacock to Be First Streamer to ...

01/04/2026

DOLBY AND DOUYIN EMPOWER THE NEXT GENERATON OF CREATORS WITH DOLBY VISION

January 4 2026, 18:00 (PST) DOLBY AND DOUYIN EMPOWER THE NEXT GENERATON OF CREATORS WITH DOLBY VISION Douyin Users Can Now Create And Share Videos With Stun...

18/03/2026

Net Insight Names Larissa GrnerMeeus CPO

Newly named chief product officer (CPO), Larissa G rner Meeus will return to Net Insight on May 4. Larissa G rner Meeus will become CPO of Net Insight on May 4...

18/03/2026

SVG Europe's The Football Summit 2026: Select Sessions Now Available to Watch on SVG PLAY

SVG Europe's The Football Summit 2026 explored how the sports broadcasting i...

18/03/2026

SVG's SportsTech@NABShow Blog Goes Live as Countdown to Vegas Heats Up

The 2026 NAB Show kicks off one month from today and SVG is once again set to cover the show from every angle. SVG's SportsTech@NAB Show Blog is now live - ...

18/03/2026

The Premiere of Dead Lover Showcases Grave Robbing and Sex With a Giant Finger

(L-R) The cast and crew of Dead Lover at The Ray Theater for its premiere at the 2025 Sundance Film Festival. (Photo by Robin Marshall/Shutterstock for Sundan...

18/03/2026

Music Row Piano from Wiltone Productions

Yamaha C7 captured in Nashville Wiltone Productions have announced the release of Music Row Piano, a deeply sampled Yamaha C7 piano library that's been ...

18/03/2026

Techivation introduce T-Warmer Mk2

Bass-enhancement plug-in upgraded Along with a steady stream of new releases, Techivation have recently been revisiting some of the older plug-ins in their ...

18/03/2026

Tonal Balance Control 3 from iZotope

Mix-reference plug-in overhauled iZotope's powerful mix-referencing plug-in has just reached its third major version, and now boasts a new capture proce...

18/03/2026

Toontrack Transistor Organ EKX

Latest EZKeys 2 expansion arrives Toontrack's staggering collection of EZKeys 2 expansions has grown once again, and the latest instalment delivers a on...

18/03/2026

Jess Ho explores the politics of food in new SBS Audio podcast For The Culture

Jess Ho explores the politics of food in new SBS Audio podcast For The Culture 18 March, 2026 Media releases New SBS Audio podcast For The Culture, hosted ...

18/03/2026

Future-ready broadcasts with ATSC 3.0 and enhanced services from Rohde & Schwarz at NAB 2026

Future-ready broadcasts with ATSC 3.0 and enhanced services from Rohde & Schwarz...

18/03/2026

LCTWS 2026

London Calling - When The Industry Convened to Help Streaming Find its MoJo In this blog, Laura Rognoni reflects on key discussions from the Connected TV World...

18/03/2026

SMPTE Unveils 2026 NAB Show Educational Presentations

SMPTE Unveils 2026 NAB Show Educational Presentations Brie Clayton March 18, 2026 0 Comments SMPTE , the home of media professionals, technologists, a...

18/03/2026

Auditel Ad Campaign Shot on Blackmagic PYXIS 12K

Auditel Ad Campaign Shot on Blackmagic PYXIS 12K Brie Clayton March 18, 2026 0 Comments LED wall virtual production blends 12K open gate acquisition w...

18/03/2026