Zika Vaccine (WEB)

FILE-In this Feb. 11, 2016 file photo, Dallas County Mosquito Lab microbiologist Spencer Lockwood sorts mosquitos collected in a trap in Hutchins, Texas, that had been set up in Dallas County near the location of a confirmed Zika virus infection.

Scientists at Wake Forest Institute for Regenerative Medicine have developed a medical tool for studying how the Zika virus may affect male fertility.

The tool, known as a human testicular organoid system, mimics the testes, including the ability to create sperm and test for toxicity.

The research was published recently in the journal Emerging Microbes & Infections.

Zika is spread to people primarily through the bites of infected Aedes aegypit mosquitoes, state health officials say. Its symptoms are fever, rash, joint pain and conjunctivitis (red eyes).

Zika also can be spread from someone who got it abroad to another person through sexual contact. Pregnant women can transmit the disease to their unborn children, which can cause birth defects.

The Associated Press reported in August that a study determined that 1 in 7 children born to U.S. mothers who were infected with Zika during pregnancy had some kind of health problem — ranging from birth defects to conditions that became apparent at a later time.

The regenerative medicine researchers found that the Zika virus can infect testicular organoids.

Researchers found a decrease in the overall viability of the cells in the infected organisms. They said that could mean multiple cell types are susceptible to cell death following Zika virus infection.

In Zika virus endemic regions, a recent study paid for by the U.S. Centers for Disease Control and Prevention demonstrated that 56 percent of blood-positive males also were sperm-positive for virus for up to 108 days after infection.

Lack of understanding of how the virus affects human testes has limited efforts to develop therapies to clear testicular infection.

“This suggests a higher contribution in disease spread and a longer infectious phase as compared to other mosquito-borne viruses,” said Dr. Hooman Sadri-Ardekani, the senior author of the study. “Little is known of the cell types that support Zika virus persistence within the human testes, and previous animal models have limitations. A human 3-D culture model is optimal to mimic human testes function.”

Sadri and his colleagues at the Wake Forest regenerative medicine institute initially reported the Zika virus effect on testes in 2017 in the journal Biology of Reproduction.

In their follow-up research, they collaborated with the Department of Tropical Medicine, Medical Microbiology, and Pharmacology at the University of Hawaii’s Burns School of Medicine.

The organoids were formed using cells from normal, adult testicular tissue. The organoids produce testosterone continuously and support limited germ-cell differentiation, partially providing the composition, diversity and function of human testes. They were slowly frozen in a cryomedia and shipped to University of Hawaii to be infected with the Zika virus.

“This organoid can be frozen and shipped to labs worldwide and opens up opportunities to test and investigate other potential testes-tropic viruses, such as Ebola,” Sadri said. “It also reduces dependency on animal models.”

Sadri and colleagues said that future research using this organoid model provides a framework for basic and translational research, including evaluation of efficacy and toxicity of anti-Zika virus drugs for clearing testicular infections.

The study was financed in part by the National Institutes of Health and the Armed Forces Institute for Regenerative Medicine. Among the co-authors is Dr. Anthony Atala, the head of the Wake Forest regenerative medicine institute.

rcraver@wsjournal.com 336-727-7376 @rcraverWSJ

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