Creative Minds: Preparing for Future Pandemics

Jonathan Abraham

Jonathan Abraham / Credit: ChieYu Lin

Growing up in Queens, NY, Jonathan Abraham developed a love for books and an interest in infectious diseases. One day Abraham got his hands on a copy of Laurie Garrett’s The Coming Plague, a 1990s bestseller warning of future global pandemics, and he sensed his life’s calling. He would help people around the world survive deadly viral outbreaks, particularly from Ebola, Marburg, and other really bad bugs that cause deadly hemorrhagic fevers.

Abraham, now a physician-scientist at Brigham and Women’s Hospital, Boston, continues to chase that dream. With support from an NIH Director’s 2016 Early Independence Award, Abraham has set out to help design the next generation of treatments to enable more people to survive future outbreaks of viral hemorrhagic fever. His research strategy: find antibodies in the blood of known survivors that helped them overcome their infections. With further study, he hopes to develop purified forms of the antibodies as potentially life-saving treatments for people whose own immune systems may not make them in time. This therapeutic strategy is called passive immunity.

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Snapshots of Life: Virus Hunting with Carbon Nanotubes

H5N2 trapped in carbon nanotubes

Credit: Penn State University

The purple pods that you see in this scanning electron micrograph are the H5N2 avian flu virus, a costly threat to the poultry and egg industry and, in very rare instances, a health risk for humans. However, these particular pods are unlikely to infect anything because they are trapped in a gray mesh of carbon nanotubes. Made by linking carbon atoms into a cylindrical pattern, such nanotubes are about 10,000 times smaller than width of a human hair.

The nanotubes above have been carefully aligned on a special type of silicon chip called a carbon-nanotube size-tunable-enrichment-microdevice (CNT-STEM). As described recently in Science Advances, this ultrasensitive device is designed to capture viruses rapidly based on their size, not their molecular characteristics [1]. This unique feature enables researchers to detect completely unknown viruses, even when they are present in extremely low numbers. In proof-of-principle studies, CNT-STEM made it possible to collect and detect viruses in a sample at concentrations 100 times lower than with other methods, suggesting the device and its new approach will be helpful in the ongoing hunt for new and emerging viruses, including those that infect people.

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Could Zika Virus Have Lasting Impact on Male Fertility?

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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Simplifying HIV Treatment: A Surprising New Lead

CD4+ cells in the gut

Caption: PET/CT imaging reveals a surprisingly high concentration (yellow, light green) of key immune cells called CD4 T cells in the colon (left) of an SIV-infected animal that received antibody infusions along with antiviral treatment. Fewer immune cells were found in the small intestine (right), while the liver (lower left) shows a high level of non-specific signal (orange).
Credit: Byrareddy et al., Science (2016).

The surprising results of an animal study are raising hopes for a far simpler treatment regimen for people infected with the AIDS-causing human immunodeficiency virus (HIV). Currently, HIV-infected individuals can live a near normal life span if, every day, they take a complex combination of drugs called antiretroviral therapy (ART). The bad news is if they stop ART, the small amounts of HIV that still lurk in their bodies can bounce back and infect key immune cells, called CD4 T cells, resulting in life-threatening suppression of their immune systems.

Now, a study of rhesus macaques infected with a close relative of HIV, the simian immunodeficiency virus (SIV), suggests there might be a new therapeutic option that works by a mechanism that has researchers both excited and baffled [1]. By teaming ART with a designer antibody used to treat people with severe bowel disease, NIH-funded researchers report that they have been able to keep SIV in check in macaques for at least two years after ART is stopped. More research is needed to figure out exactly how the new strategy works, and whether it would also work for humans infected with HIV. However, the findings suggest there may be a way to achieve lasting remission from HIV without the risks, costs, and inconvenience associated with a daily regimen of drugs.

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Treating Zika Infection: Repurposed Drugs Show Promise

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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