Caption: Immunofluorescence staining showing that the testes of Zika-free mice (left) are full of developing sperm (pink), while the testes of Zika-infected mice (right) contain very few sperm. Credit: Prabagaran Esakky, Washington University School of Medicine, St. Louis
Recent research has shown that the mosquito-borne Zika virus has the potential to cause serious health problems, including severe birth defects in humans. But the damaging effects of Zika might not end there: results of a new mouse study show that the virus may also have an unexpected negative—and possibly long-lasting—impact on male fertility.
In work published in the journal Nature, an NIH-funded research team found that Zika infections can persist for many weeks in the reproductive systems of male mice . As a result of this infection, levels of testosterone and other sex hormones drop, sperm counts fall, and, in some animals, the testicles shrink to 1/10th of their normal size, possibly irreversibly. All of this adds up to Zika-infected male mice that are significantly less fertile than their healthy counterparts—producing about a quarter as many viable offspring as normal when mated with female mice. While mice are certainly not humans, the results underscore the urgent need for additional research to examine the full spectrum of Zika’s health effects in men, women, and children of both sexes.
Caption: An NCATS researcher dispenses Zika virus into trays for compound screening in a lab using procedures that follow strict biosafety standards. Credit: National Center for Advancing Translational Sciences, NIH
In response to the health threat posed by the recent outbreak of Zika virus in Latin America and its recent spread to Puerto Rico and Florida, researchers have been working at a furious pace to learn more about the mosquito-borne virus. Considerable progress has been made in understanding how Zika might cause babies to be born with unusually small heads and other abnormalities and in developing vaccines that may guard against Zika infection.
Still, there remains an urgent need to find drugs that can be used to treat people already infected with the Zika virus. A team that includes scientists at NIH’s National Center for Advancing Translational Sciences (NCATS) now has some encouraging news on this front. By testing 6,000 FDA-approved drugs and experimental chemical compounds on Zika-infected human cells in the lab, they’ve shown that some existing drugs might be repurposed to fight Zika infection and prevent the virus from harming the developing brain . While additional research is needed, the new findings suggest it may be possible to speed development and approval of new treatments for Zika infection.
Caption: Zika virus (red), isolated from a microcephaly case in Brazil. The virus is associated with cellular membranes in the center. Credit: NIAID
Last February, the World Health Organization declared a public health emergency over concerns about very serious birth defects in Brazil and their possible link to Zika virus. But even before then, concerns about the unprecedented spread of Zika virus in Brazil and elsewhere in Latin America had prompted NIH-funded scientists to step up their efforts to combat this emerging infectious disease threat. Over the last year, research aimed at understanding the mosquito-borne virus has progressed rapidly, and we now appear to be getting closer to a Zika vaccine.
In a recent study in the journal Nature, researchers found that a single dose of either of two experimental vaccines completely protected mice against a major viral strain responsible for the Zika outbreak in Brazil . Caution is certainly warranted when extrapolating these (or any other) findings from mice to people. But, taking into account the fact that researchers have already developed safe and effective human vaccines for several related viruses, the new work represents a very encouraging milestone on the road toward a much-needed Zika vaccine for humans.
Credit: David Goodsell, The Scripps Research Institute
This lively interplay of shape and color is an artistic rendering of the Zika virus preparing to enter a cell (blue) by binding to its protein receptors (green). The spherical structures (pink) represent two Zika viruses in a blood vessel filled with blood plasma cells (tan). The virus in the middle in cross section shows viral envelope proteins (red) studding the outer surface, with membrane proteins (pink) embedded in a fatty layer of lipids (light purples). In the innermost circle, you can see the viral genome (yellow) coiled around capsid proteins (orange).
This image was sketched and hand-painted with watercolors by David Goodsell, a researcher and illustrator at The Scripps Research Institute, La Jolla, CA. Goodsell put paint and science to paper as part of the “Molecule of the Month” series run by RCSB Protein Data Bank (PDB), which NIH co-supports with the National Science Foundation and the Department of Energy. The PDB, which contains structural data on thousands of proteins and small molecules, uses its “Molecule of the Month” series to help students visualize a molecule or virus and to encourage their exploration of structural biology and its applications to medicine.
Caption: Human neural progenitor cells (gray) infected with Zika virus (green) increased the enzyme caspase-3 (red), suggesting increased cell death. Credit: Sarah C. Ogden, Florida State University, Tallahassee
Recently, public health officials have raised major concerns over the disturbing spread of the mosquito-borne Zika virus among people living in and traveling to many parts of Central and South America . While the symptoms of Zika infection are typically mild, grave concerns have arisen about its potential impact during pregnancy. The concerns stem from the unusual number of births of children with microcephaly, a very serious condition characterized by a small head and damaged brain, coinciding with the spread of Zika virus. Now, two new studies strengthen the connection between Zika and an array of birth defects, including, but not limited to, microcephaly.
In the first study, NIH-funded laboratory researchers show that Zika virus can infect and kill human neural progenitor cells . Those progenitor cells give rise to the cerebral cortex, a portion of the brain often affected in children with microcephaly. The second study, involving a small cohort of women diagnosed with Zika virus during their pregnancies in Rio de Janeiro, Brazil, suggests that the attack rate is disturbingly high, and microcephaly is just one of many risks to the developing fetus.