U.S. academics test new mouse model for possible Zika vaccine

Aedes aegypti mosquito, which can spread Zika virus  

A research team at Washington University School of Medicine has established a new mouse model for testing vaccines and therapeutics that can battle Zika virus after discovering that the mice mimic the way humans are infected. 

The new research, published this week in Cell Host & Microbe, showed that these mice carry high levels of the virus in their brain and spinal cord, consistent with evidence showing that Zika causes neurological defects in human fetuses. 

The researchers also detected the highest levels of the virus in the testes of male mice--a finding that supports clinical data indicating the virus can be sexually transmitted.

"Now that we know the mice can be vulnerable to Zika infection, we can use the animals to test vaccines and therapeutics--and some of those studies are already underway--as well as to understand the pathogenesis of the virus," said senior author Michael Diamond, a professor of medicine at Washington University, in a university news release.

The new model of Zika virus infection, along with another recently identified by scientists at the University of Texas Medical Branch, are the first to be developed since 1976. The earlier models were not as clinically relevant because the infections were generated by injecting the virus directly into the brain. In the new models, infection occurs via the skin, much like the bite of the mosquito that spreads the virus.

The ongoing Zika virus outbreak in Latin America and the Caribbean has created an urgent need for identifying small animal models as a first step toward developing vaccines and treatments to fight the infection. 

The infection has been linked to microcephaly, a condition in which infants are born with unusually small heads and brain damage. In adults, the virus is thought to be related to rare cases of Guillain-Barré syndrome, an illness that can cause temporary paralysis.

For the new study, researchers in Diamond's laboratory, led by first author Helen Lazear, now at the University of North Carolina at Chapel Hill, tested five strains of the Zika virus in the mice: the original strain acquired from Uganda in 1947; three strains that circulated in Senegal in the 1980s; and the French Polynesian strain, which caused infections in 2013 and is nearly identical to the strain causing the current outbreak. 

All yielded similar results in the animals, suggesting that there may not be much difference in the pathogenicity between individual strains, at least in this mouse model. Tests with the viral strains from the current Zika outbreak are ongoing.

"It appears that pregnant women infected with Zika can pass the virus to babies in utero and that newborns also may be susceptible to infection," added Diamond, also an associate director of the university's Center for Human Immunology and Immunotherapy Programs. 

"Other than in infants, we don't really see severe disease in most people with Zika, except for a small fraction who develop Guillain-Barré."

As new clinical information becomes available about the virus in humans, Diamond has pivoted his research to investigate suspected links in mice.

"We looked for evidence of Zika in the mouse testes mostly as an afterthought, due to mounting evidence of sexual transmission and were surprised that viral levels were the highest we saw in any tissue," Diamond noted. "We are now doing subsequent tests to determine how long those viral levels are sustained, which could help us estimate the length of time Zika can be transmitted sexually."

- here's the university news release
- see the Cell research paper (PDF)