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Three-way molecular bond may be key to Zika-induced birth defects
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Zika virus’ ability to cause birth defects may lie, at least in part, in its prowess bonding with two particular molecules, according to a study.
A team at the Scripps Research Institute’s Florida campus found that one of the molecules, AXL receptor tyrosine kinase, may enable Zika to penetrate a placental barrier that is closed to other flaviviruses and cause congenital defects including microcephaly, eye and joint injury, and brain damage. The team recently published its findings in Proceedings of the National Academy of Sciences.
“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,” study leader Hyeryun Choe, PhD, said in a news release.
Choe and colleagues found that Zika penetrated human umbilical endothelial cells far more often than two of its close relatives, dengue and West Nile viruses.
The study found that Zika’s viral counts in human umbilical endothelial cells measured as high as 100 or 1,000 times those of dengue and West Nile.
AXL further aids Zika by protecting it from the fetus’ immune response, the researchers added.
“The physiological function of AXL is to quench activated immune reactions, including the antiviral interferon response,” study researcher Audrey S. Richard, PhD, said in the release.
“By using AXL, Zika virus catches two birds with one stone. It enters cells and also gains a favorable environment for its replication inside the cells.”
A key to the Zika-AXL marriage, the researchers said, is growth arrest-specific protein 6 (Gas6), a molecule found in body fluids that binds the virus and AXL on opposite ends of itself.
It is unclear why Zika is so adept at allying with AXL whereas other flaviviruses are not. But study researcher Byoung-Shik Shim, PhD, noted that “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 explained that AXL is present in the blood-brain and blood-eye barriers, as well as the testes.
Zika could exploit AXL in those places, they suggested, explaining the disease’s infections of the brain and eyes and its ability to be transmitted sexually. — by Joe Green
Reference:
Richard AS, et al. Proc Natl Acad Sci USA. 2017;doi:10.1073/pnas.1620558114.
Disclosure: Diamond reports that he is a consultant at InBios, Sanofi Pasteur, Takeda Pharmaceuticals and Visterra, serves on the scientific advisory boards of Moderna and OraGene and is the recipient of research grants from Moderna, Sanofi Pasteur and Visterra.