Health
A new look inside Ebola’s “viral factories”
Two views of Ebola’s “viral factories” inside host cells. The image on the left was captured via confocal immunofluorescence microscopy and shows Ebola’s viral factories in pink. The image on the right was captured using electron tomography and shows viral factories in orange.
Newswise — LA JOLLA, CA—New research in the journal Nature Communications gives scientists an important window into how Ebola virus replicates inside host cells. The study, led by scientists at La Jolla Institute for Immunology (LJI), reveals the inner workings of “viral factories,” clusters of viral proteins and genomes that form in host cells.
The research team, which included experts from Scripps Research and UC San Diego School of Medicine, found that Ebola virus’s replication machinery forms fascinating microscopic structures that become viral factories. By understanding the architecture and function of these microscopic manufacturing hubs, researchers may be closer to developing new therapies that interrupt the Ebola virus life cycle and prevent severe disease.
“We are imaging these fluid and dynamic assembly centers for the first time. Understanding how they work and what they require gives us the information needed to defeat them,” says LJI President and CEO Erica Ollmann Saphire, Ph.D., senior author of the new study.
What is a viral factory?
Scientists first spotted what would turn out to be “virus factories” in virus-infected animal cells back in the 1960s, but they didn’t know what they were seeing. Within a sea of normal cellular proteins, these areas looked like fuzzy splotches.
“People had already seen that Ebola-infected cells had these ‘inclusions,’” says LJI Postdoctoral Researcher Jingru Fang, Ph.D., first author of the new study. For a long time, scientists thought of these “inclusions” as helpful visual indicators of infection, without understanding their true purpose. “But in fact, these ‘inclusion bodies’ actively gather an enormous quantity of viral proteins and viral RNAs.”
Many viral pathogens, including rabies virus and RSV (respiratory syncytial virus) form inclusions in host cells, Fang explains. “Recent studies suggest that these cellular inclusions are the site where viruses make their RNA genomes. They are ‘viral factories’ with actual functional purpose: to offer a secured space for viral RNA synthesis,” says Fang. “The process of viral RNA synthesis involves flux of viral building blocks. This means molecules gathered inside viral factories should be able to move freely rather than being static.”
For the new study, Saphire, Fang and their colleagues wondered: Can we observe the movement of viral building blocks directly in living cells?
Fang began by tagging a viral protein called VP35 with a fluorescent marker that makes the protein glow in the dark. VP35 is a critical component of the viral factory and is important for viral RNA synthesis (and the making of new copies of Ebola virus). Working with imaging experts in the LJI Microscopy and Histology Core, Fang followed the glowing proteins in live cells, which express a simplified and non-infectious version of Ebola viral factories.
Under the microscope, Fang and colleagues could indeed see and even measure how molecules move inside the viral factories formed in host cells. This finding added evidence that viral proteins are clumping together like droplets so they can churn out the proteins needed to help the virus replicate. Those mysterious inclusions really are viral factories. The researcher dubbed these “droplet-like” viral factories.
Then the scientists saw something odd. Some of the glowing proteins didn’t gather into clumps. Instead, they joined up with a smattering of other viral proteins, creating a fluorescent swirl that evoked van Gogh’s “Starry Night.” These trails of viral proteins still had the right ingredients to replicate Ebola virus, so the scientists dubbed them “network-like” viral factories.
“These are two different flavors of the viral factory,” says Fang. “People have mostly focused on the droplet-like form, which is the majority, and not paid too much attention to this other form.”
Besides their shapes, there was a key difference between the two factories. It appeared the network-like factories had the right ingredients for the incoming Ebola virus to express its genes, but they didn’t actually produce virus progenies.
A multi-tasking machine
Next, the researchers looked at a key player in infection: a protein called virus polymerase. Polymerase is a multifunctional nanomachine that comes with the virus. This machine not only copies the Ebola virus genomic material, it also transcribes the viral genome into messenger RNAs, which instruct infected cells to produce loads of viral proteins. The researchers wanted to understand how this viral machine functions inside viral factories.
Ebola virus polymerase is already known as a hard-working protein—all Ebola viral proteins have to be. Ebola virus is a highly efficient pathogen because it gets by with just seven genes (humans have more than 20,000 genes). Saphire has led research showing that Ebola virus survives by making proteins that can transform and take on different jobs during the course of infection.
Just last year, Saphire, Fang, and collaborators published a related discovery that viral polymerase actually harnesses a druggable human protein to help the virus replicate its genome. The team reported that while polymerase is essential for viral replication, the polymerase doesn’t actually jump into action until infection is well underway.
This work was important for understanding how polymerase stepped into action, but scientists also needed to know where polymerase was active. Fang knew it would be important to look at what polymerase might be up to in viral factories.
The researchers discovered that polymerase actually builds its own special structures inside viral factories. Many copies of polymerase gather in small bundles, called foci. The researchers found that these bundles spread out when a droplet-like viral factory starts replicating viral material.
Scientists aren’t sure exactly why polymerase needs to form bundles before it can do its job, but the spatial arrangement of the bundles must be important. As Fang points out, the idea of many small components coming together to build a structure isn’t a new concept in nature. “You can use a beehive or coral reef as the analogy to help understand why a specific spatial arrangement is important for a biological system to function,” she says.
With this finding, scientists now know how to find different kinds of viral factories and how polymerase organizes itself down on the factory floor.
Fighting back
More than 30 human pathogens are known to assemble viral factories inside host cells, including respiratory syncytial virus (RSV) and even rabies virus. With this new view of Ebola’s viral factories, the scientists are curious whether other viruses construct similar forms of viral factories—and whether other viruses use their own versions of polymerase in the same way.
“If that’s true, maybe we can target the feature of viral factory formation that has been shared by multiple different viruses,” says Fang.
Going forward, Fang would also like to study how Ebola virus forms viral factories in different kinds of host cells. Do these viral factories look different in cells from animals (such as the virus’s natural hosts, the fruit bats) that can carry the virus around without getting sick? “Can we find some explanation for host-specific viral pathogenesis?” she asks.
The new study also demonstrates the importance of collaboration across San Diego’s Torrey Pines Mesa. The LJI team worked closely with Scripps Research Professor Ashok Deniz, Ph.D., and UC San Diego Professor Mark H. Ellisman, Ph.D., Director of the National Center for Microscopy and Imaging Research.
“The combination of state-of-the-art tools available on the Torrey Pines Mesa allowed us to combine the biophysical characterization with the human health insight,” says Saphire
Additional authors of the study, “Spatial and functional arrangement of Ebola virus polymerase inside phase-separated viral factories,” include Guillaume Castillon, Sebastien Phan, Sara McArdle, Chitra Hariharan, and Aiyana Adams.
This study was supported by the National Institute of Health (grants NIH S10OD021831, R24GM137200, and S10OD021784), an Imaging Scientist grant (2019‐198153) from the Chan Zuckerberg Initiative, LJI institutional funds, and the Donald E. and Delia B. Baxter Foundation Fellowship.
DOI: 10.1038/s41467-023-39821-7
Source: La Jolla Institute for Immunology
About La Jolla Institute
The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease. Visit lji.org for more information.
Journal Link: Nature Communication, July-2023
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Take steps to limit risk for cardiovascular disease
(Family Features) The last decade has seen a surge in cardiovascular risk factors such as uncontrolled high blood pressure, diabetes and obesity, each of which raises the risks of developing heart disease and stroke. These trends are leading researchers to conclude that the prevalence of cardiovascular disease (CVD) will continue to rise.
More than 60% of U.S. adults will have some type of CVD by 2050, according to forecasted projections from the American Heart Association, which is celebrating 100 years of lifesaving service as the world’s leading nonprofit organization focused on heart and brain health for all. Additionally, total costs related to CVD are expected to nearly triple in that time to more than $1.8 trillion.
The increase will be driven by an older, more diverse population, but these risk factors are rising even among children and adults.
“We recognize the landscape of cardiovascular health will change over the next three decades because of the coming tsunami of rising health care costs, an older population living longer and increasing numbers of people from under-resourced populations,” said American Heart Association volunteer Karen E. Joynt Maddox, M.D., M.P.H., FAHA. “Yet these are still leading causes of death and disability in the U.S.”
While continued systematic changes are needed in science, policy and health care, the majority of CVD is preventable at an individual level. You can help turn the tide on the dire outlook of CVD while improving your own health by following and encouraging others to follow the American Heart Association’s “Life’s Essential 8.”
Quest for Living Healthier
Eat better. Aim for an overall healthy eating pattern including whole foods, fruits and vegetables, lean protein, nuts, seeds and cooking with olive and canola oils.
Be active. Adults should get 2 1/2 hours of moderate or 75 minutes of vigorous physical activity per week. Kids should have 60 minutes every day, including play and structured activities.
Quit tobacco. Use of inhaled nicotine delivery products, which includes traditional cigarettes, electronic cigarettes and vaping, is the leading cause of preventable death in the U.S.
Get healthy sleep. Most adults need 7-9 hours of sleep each night. Children require 10-16 hours for ages 5 and younger, including naps; 9-12 hours for ages 6-12; and 8-10 hours for ages 13-18.
Manage weight. Achieving and maintaining a healthy weight has many benefits. Body mass index is a useful gauge. Optimal BMI is less than 25, but less than 18.5 is considered underweight. You can calculate it online or consult a health care professional.
Control cholesterol. High levels of non-HDL, or “bad,” cholesterol can lead to heart disease. Your health care professional can consider non-HDL cholesterol as the preferred number to monitor, rather than total cholesterol, because it can be measured without fasting beforehand and is reliably calculated among all people.
Manage blood sugar. Most of the food you eat is turned into glucose (or blood sugar) your body uses as energy. Over time, high levels of blood sugar can damage your heart, kidneys, eyes and nerves.
Manage blood pressure. Keeping your blood pressure within acceptable ranges can keep you healthier longer. Levels less than 120/80 mm Hg are optimal. High blood pressure is defined as 130-139 mm Hg systolic pressure (the top number in a reading) or 80-89 mm Hg diastolic pressure (bottom number).
Find more ways to manage your health in the new year and beyond at heart.org.
Photo courtesy of Shutterstock
SOURCE:
American Heart Association
Our Lifestyle section on STM Daily News is a hub of inspiration and practical information, offering a range of articles that touch on various aspects of daily life. From tips on family finances to guides for maintaining health and wellness, we strive to empower our readers with knowledge and resources to enhance their lifestyles. Whether you’re seeking outdoor activity ideas, fashion trends, or travel recommendations, our lifestyle section has got you covered. Visit us today at https://stmdailynews.com/category/lifestyle/ and embark on a journey of discovery and self-improvement.
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As autumn settles in and November draws near, it’s time to embrace a cause that calls for solidarity, conversation, and awareness: No Shave November! This year, the American Cancer Fund invites everyone—from athletes and coaches to military personnel, veterans, students, and everyday individuals—to join our efforts in raising awareness about cancer through facial hair.
What is No Shave November?
No Shave November is not just about letting your beard grow; it’s a powerful initiative aimed at promoting cancer awareness and encouraging conversations about prevention and early detection. Students, professionals, and community members can stand together to support the next generation’s campaign, “Screamin for Screenings.” By participating, we can unite our voices and show our commitment to fighting cancer.
Why Participate?
Cancer affects millions of people and their families every year. By participating in No Shave November, you can help bring the issue to the forefront and make a difference in your community. Not only do we aim to create a visual representation of support, but we also want to generate important conversations about cancer prevention. Growing facial hair becomes a symbol of solidarity and awareness, as each beard and mustache serves as a conversation starter for discussing vital topics related to health and wellbeing.
How You Can Get Involved
1. Sign Up!
Head over to our website and register for the campaign. Once signed up, you’ll receive a toolkit with resources to help you promote awareness among your friends and family. Join us here!
2. Spread the Word
Share your No Shave November journey on social media using the hashtag #NoShaveNovember and tag the American Cancer Fund on Instagram, Facebook, and X. Your posts can inspire others and create a ripple effect of awareness across platforms.
3. Fundraise
In addition to growing your facial hair, consider setting up a fundraising page to collect donations for cancer research and support services. Every contribution counts and can make a significant impact on the lives of those affected by cancer. Start fundraising here!
Make Every Hair Count
This November, let’s band together and show that every hair can represent strength, resilience, and awareness in the fight against cancer. Engaging with your community and initiating conversations about cancer prevention and screening can lead to life-saving actions. Whether you sport a full beard, a mustache, or just go for the stubble, remember—the goal is to spread awareness and support those affected by this disease.
Join us in our mission to make a difference, one hair at a time. Together, we can shine a light on the importance of cancer awareness, prevention, and early detection. Let’s get growing and make No Shave November a month to remember!
For more information about No Shave November and how to participate, please visit American Cancer Fund and be part of the movement that unites us all in the fight against cancer!
Together we can make a difference.
SOURCE American Cancer Fund
Our Lifestyle section on STM Daily News is a hub of inspiration and practical information, offering a range of articles that touch on various aspects of daily life. From tips on family finances to guides for maintaining health and wellness, we strive to empower our readers with knowledge and resources to enhance their lifestyles. Whether you’re seeking outdoor activity ideas, fashion trends, or travel recommendations, our lifestyle section has got you covered. Visit us today at https://stmdailynews.com/category/lifestyle/ and embark on a journey of discovery and self-improvement.
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Lifestyle
Some people love to scare themselves in an already scary world − here’s the psychology of why
Experiencing controlled fear can enhance social bonds, increase resilience, and offer psychological benefits, making horror entertainment a healthy distraction from scary real-life terrors.
Fall for me as a teenager meant football games, homecoming dresses – and haunted houses. My friends organized group trips to the local fairground, where barn sheds were turned into halls of horror, and masked men nipped at our ankles with (chainless) chain saws as we waited in line, anticipating deeper frights to come once we were inside.
I’m not the only one who loves a good scare. Halloween attractions company America Haunts estimates Americans are spending upward of US$500 million annually on haunted house entrance fees simply for the privilege of being frightened. And lots of fright fans don’t limit their horror entertainment to spooky season, gorging horror movies, shows and books all year long.
To some people, this preoccupation with horror can seem tone deaf. School shootings, child abuse, war – the list of real-life horrors is endless. Why seek manufactured fear for entertainment when the world offers real terror in such large quantities?
As a developmental psychologist who writes dark thrillers on the side, I find the intersection of psychology and fear intriguing. To explain what drives this fascination with fear, I point to the theory that emotions evolved as a universal experience in humans because they help us survive. Creating fear in otherwise safe lives can be enjoyable – and is a way for people to practice and prepare for real-life dangers.
Fear can feel good
Controlled fear experiences – where you can click your remote, close the book, or walk out of the haunted house whenever you want – offer the physiological high that fear triggers, without any real risk.
When you perceive yourself under threat, adrenaline surges in your body and the evolutionary fight-or-flight response is activated. Your heart rate increases, you breathe deeper and faster, and your blood pressure goes up. Your body is preparing to defend itself against the danger or get away as fast as possible.
This physical reaction is crucial when facing a real threat. When experiencing controlled fear – like jump scares in a zombie TV show – you get to enjoy this energized sensation, similar to a runner’s high, without any risks. And then, once the threat is dealt with, your body releases the neurotransmitter dopamine, which provides sensations of pleasure and relief.
In one study, researchers found that people who visited a high-intensity haunted house as a controlled fear experience displayed less brain activity in response to stimuli and less anxiety post-exposure. This finding suggests that exposing yourself to horror films, scary stories or suspenseful video games can actually calm you afterward. The effect might also explain why my husband and I choose to relax by watching zombie shows after a busy day at work.
The ties that bind
An essential motivation for human beings is the sense of belonging to a social group. According to the surgeon general, Americans who miss those connections are caught up in an epidemic of loneliness, which leaves people at risk for mental and physical health issues.
Going through intense fear experiences together strengthens the bonds between individuals. Good examples include veterans who served together in combat, survivors of natural disasters, and the “families” created in groups of first responders.
I’m a volunteer firefighter, and the unique connection created through sharing intense threats, such as entering a burning building together, manifests in deep emotional bonds with my colleagues. After a significant fire call, we often note the improved morale and camaraderie of the firehouse. I feel a flood of positive emotions anytime I think of my firefighting partners, even when the events occurred months or years ago.
Controlled fear experiences artificially create similar opportunities for bonding. Exposure to stress triggers not only the fight-or-flight response, but in many situations it also initiates what psychologists call the “tend-and-befriend” system. A perceived threat prompts humans to tend to offspring and create social-emotional bonds for protection and comfort. This system is largely regulated by the so-called “love hormone” oxytocin.
The tend-and-befriend reaction is particularly likely when you experience stress around others with whom you have already established positive social connections. When you encounter stressors within your social network, your oxytocin levels rise to initiate social coping strategies. As a result, when you navigate a recreational fear experience like a haunted house with friends, you are setting the emotional stage to feel bonded with the people beside you.
Sitting in the dark with friends while you watch a scary movie or navigating a haunted corn maze with a date is good for your health, in that it helps you strengthen those social connections.
An ounce of prevention = a pound of cure
Controlled fear experiences can also be a way for you to prepare for the worst. Think of the early days of the COVID-19 pandemic, when the films “Contagion” and “Outbreak” trended on streaming platforms as people around the world sheltered at home. By watching threat scenarios play out in controlled ways through media, you can learn about your fears and emotionally prepare for future threats.
For example, researchers at Aarhus University’s Recreational Fear Lab in Denmark demonstrated in one study that people who regularly consumed horror media were more psychologically resilient during the COVID-19 pandemic than nonhorror fans. The scientists suggest that this resilience might be a result of a kind of training these fans went through – they practiced coping with the fear and anxiety provoked by their preferred form of entertainment. As a result, they were better prepared to manage the real fear triggered by the pandemic.
When I’m not teaching, I’m an avid reader of crime fiction. I also write psychological thrillers under the pen name Sarah K. Stephens. As both a reader and writer, I notice similar themes in the books I am drawn to, all of which tie into my own deep-rooted fears: mothers who fail their children somehow, women manipulated into subservience, lots of misogynist antagonists.
I enjoy writing and reading about my fears – and seeing the bad guys get their just desserts in the end – because it offers a way for me to control the story. Consuming these narratives lets me mentally rehearse how I would handle these kinds of circumstances if any were to manifest in my real life.
Survive and thrive
In the case of controlled fear experiences, scaring yourself is a pivotal technique to help you survive and adapt in a frightening world. By eliciting powerful, positive emotions, strengthening social networks and preparing you for your worst fears, you’re better able to embrace each day to its fullest.
So the next time you’re choosing between an upbeat comedy and a creepy thriller for your movie night, pick the dark side – it’s good for your health.
Sarah Kollat, Teaching Professor of Psychology, Penn State
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Our Lifestyle section on STM Daily News is a hub of inspiration and practical information, offering a range of articles that touch on various aspects of daily life. From tips on family finances to guides for maintaining health and wellness, we strive to empower our readers with knowledge and resources to enhance their lifestyles. Whether you’re seeking outdoor activity ideas, fashion trends, or travel recommendations, our lifestyle section has got you covered. Visit us today at https://stmdailynews.com/category/lifestyle/ and embark on a journey of discovery and self-improvement.
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