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Looking to Llamas for New Ways to Fight the Flu

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Lllama nanobodiesResearchers are making tremendous strides toward developing better ways to reduce our risk of getting the flu. And one of the latest ideas for foiling the flu—a “gene mist” that could be sprayed into the nose—comes from a most surprising source: llamas.

Like humans and many other creatures, these fuzzy South American relatives of the camel produce immune molecules, called antibodies, in their blood when exposed to viruses and other foreign substances. Researchers speculated that because the llama’s antibodies are so much smaller than human antibodies, they might be easier to use therapeutically in fending off a wide range of flu viruses. This idea is now being leveraged to design a new type of gene therapy that may someday provide humans with broader protection against the flu [1].

A Lean, Mean DNA Packaging Machine

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Three views of bacteriophage T4

Credit: Victor Padilla-Sanchez, The Catholic University of America, Washington, D.C.

All plants and animals are susceptible to viral infections. But did you know that’s also true for bacteria? They get nailed by viruses called bacteriophages, and there are thousands of them in nature including this one that resembles a lunar lander: bacteriophage T4 (left panel). It’s a popular model organism that researchers have studied for nearly a century, helping them over the years to learn more about biochemistry, genetics, and molecular biology [1].

The bacteriophage T4 infects the bacterium Escherichia coli, which normally inhabits the gastrointestinal tract of humans. T4’s invasion starts by touching down on the bacterial cell wall and injecting viral DNA through its tube-like tail (purple) into the cell. A DNA “packaging machine” (middle and right panels) between the bacteriophage’s “head” and “tail” (green, yellow, blue spikes) keeps the double-stranded DNA (middle panel, red) at the ready. All the vivid colors you see in the images help to distinguish between the various proteins or protein subunits that make up the intricate structure of the bacteriophage and its DNA packaging machine.

Twinkle, Twinkle Little Cryo-EM Star

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The stars are out and shining this holiday season. But there are some star-shaped structures now under study in the lab that also give us plenty of reason for hope. One of them is a tiny virus called bacteriophage phi-6, which researchers are studying in an effort to combat a similar, but more-complex, group of viruses that can cause life-threatening dehydration in young children.

Thanks to a breakthrough technology called cryo-electron microscopy (cryo-EM), NIH researchers recently captured, at near atomic-level of detail, the 3D structure of this immature bacteriophage phi-6 particle in the process of replication. At the points of its “star,” key proteins (red) are positioned to transport clipped, single-stranded segments of the virus’ own genetic information into its newly made shell, or procapsid (blue). Once inside the procapsid, an enzyme (purple) will copy the segments to make the genetic information double-stranded, while another protein (yellow) will help package them. As the procapsid matures, it undergoes dramatic structural changes.

Creative Minds: Preparing for Future Pandemics

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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.

Snapshots of Life: Virus Hunting with Carbon Nanotubes

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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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