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Zika virus

Francis Collins visits Ziika Forest

Caption: Here I am visiting the Ziika Forest area of Uganda, where the Zika virus was first identified in 1947.
Credit: National Institutes of Health

A couple of summers ago, the threat of mosquito-borne Zika virus disease in tropical areas of the Americas caused major concern, and altered the travel plans of many. The concern was driven by reports of Zika-infected women giving birth to babies with small heads and incompletely developed brains (microcephaly), as well as other serious birth defects. So, with another summer vacation season now upon us, you might wonder what’s become of Zika.

While pregnant women and couples planning on having kids should still take extra precautions [1] when travelling outside the country, the near-term risk of disease outbreaks has largely subsided because so many folks living in affected areas have already been exposed to the virus and developed protective immunity. But the Zika virus—first identified in the Ziika Forest in Uganda in 1947—has by no means been eliminated, making it crucial to learn more about how it spreads to avert future outbreaks. It’s very likely we have not heard the last of Zika in the Western hemisphere.

Recently, an international research team, partly funded by NIH, used genomic tools to trace the spread of the Zika virus. Genomic analysis can be used to build a “family tree” of viral isolates, and such analysis suggests that the first Zika cases in Central America were reported about a year after the virus had actually arrived and begun to spread.

The Zika virus, having circulated for decades in Africa and Asia before sparking a major outbreak in French Polynesia in 2013, slipped undetected across the Pacific Ocean into Brazil early in 2014, as established in previous studies. The new work reveals that by that summer, the bug had already hopped unnoticed to Honduras, spreading rapidly to other Central American nations and Mexico—likely by late 2014 and into 2015 [2].

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MinION sequencing device

Caption: MinION sequencing device plugged into a laptop/Oxford Nanopore Technologies

It’s hard to believe, but it’s been almost 15 years since we successfully completed the Human Genome Project, ahead of schedule and under budget. I was proud to stand with my international colleagues in a celebration at the Library of Congress on April 14, 2003 (which happens to be my birthday), to announce that we had stitched together the very first reference sequence of the human genome at a total cost of about $400 million. As remarkable as that achievement was, it was just the beginning of our ongoing effort to understand the human genome, and to use that understanding to improve human health.

That first reference human genome was sequenced using automated machines that were the size of small phone booths. Since then, breathtaking progress has been made in developing innovative technologies that have made DNA sequencing far easier, faster, and more affordable. Now, a report in Nature Biotechnology highlights the latest advance: the sequencing and assembly of a human genome using a pocket-sized device [1]. It was generated using several “nanopore” devices that can be purchased online with a “starter kit” for just $1,000. In fact, this new genome sequence—completed in a matter of weeks—includes some notoriously hard-to-sequence stretches of DNA, filling several key gaps in our original reference genome.

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zika-histology

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 [1]. 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.

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Zika researcher

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 [1]. While additional research is needed, the new findings suggest it may be possible to speed development and approval of new treatments for Zika infection.

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Zika Virus

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 [1]. 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.

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