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
Author
Discover more from Daily News
Subscribe to get the latest posts sent to your email.
health and wellness
6 Ways to Build Lasting Healthy Habits
Starting on a path toward healthy habits is often easier than maintaining them long term. This year, you can avoid a major pitfall of healthy resolutions and build healthy habits that stick by working small, positive steps into your daily life.
(Family Features) Starting on a path toward healthy habits is often easier than maintaining them long term. This year, you can avoid a major pitfall of healthy resolutions and build healthy habits that stick by working small, positive steps into your daily life.
In fact, healthy habits are the first suggested treatment strategy for people whose blood pressure and cholesterol levels are creeping higher than normal, according to an American Heart Association scientific statement.
“The current guidelines for managing high blood pressure and cholesterol recognize that otherwise healthy individuals with mildly or moderately elevated levels of these cardiovascular risk factors should actively attempt to reduce these risks, and increasing physical activity is a great place to start,” said Bethany Barone Gibbs, Ph.D., chair of the statement writing group and chair of the department of epidemiology and biostatistics at West Virginia University School of Public Health.
These six ideas from the American Heart Association’s Healthy for Good Habit Coach can help.
Bust Common Habit-Building Myths
You may be surprised to learn the truth about creating and sticking to healthy habits. One myth is getting healthy means doing things you don’t like. Research shows positive emotions make habits stick, so set your intentions on something you enjoy. Another misconception is big results require big changes, which may lead to overly ambitious habits. However, the simpler the routine is, the more likely it is to become habit.
Work with Your “Brain Loops”
Your brain creates “loops” for habits made up of three things: a cue, a routine and a reward. Each time the loop is repeated, it becomes more routine and may become automatic. Knowing this, you can design cues for developing new, healthy habits, such as setting walking shoes by the bed to start a walking habit. The routine is putting on the shoes and walking around the block, and the reward is the pleasant sensations and brighter mood from a morning stroll.
Create Cues That Work for You
Most successful health habits begin with a cue. The cue can be external in your environment or internal in terms of your mindset. The more consistent the cue, the more likely it is to trigger the habit. Hacking your brain’s reminder system can help you remember your cue. Some examples of visual cues are placing a sticky note where you’ll see it often, keeping a water bottle on your desk or refrigerating fresh veggies at eye level.
Build a Routine That Supports Your Goals
Positive and consistent habits are important to achieve your personal goals. Small habits done consistently can add up to big results. To create a new healthy habit, think through the steps that could lead to your desired outcome. Ask yourself whether you want to do it, if it’s easy and if it’s high impact. It’s important to choose habits that make a difference and move you closer to your goals.
For example, if one of your goals is improving your heart health, a meaningful habit might be to move more. Increasing physical activity can help lower blood pressure and cholesterol along with many other health benefits, Gibbs said.
“Every little bit of activity is better than none,” she said. “Even small initial increases of 5-10 minutes a day can yield health benefits.”
Use Rewards to Make Habits Stick
Start by choosing a habit you enjoy that’s rewarding by itself. If you’re more of a dancer than runner, increase your physical activity with an upbeat dance class. You might also look for a more enjoyable version of a new habit, such as getting more fruits and veggies by sipping on a delicious smoothie.
Understand Resets are Part of the Process
New habits are experiments. If they don’t stick, you haven’t failed. Instead, you’ve learned what doesn’t work, which is useful. Get curious and ask yourself which part of the habit didn’t work for you. Maybe the cue was ineffective. Maybe the steps of the routine were too ambitious and you need to split them into smaller, easier steps. If you realize you don’t enjoy the habit, stop doing it and try something else.
Find more inspiration and ideas to jumpstart healthy habits this year at heart.org/habits.
Photos courtesy of Getty Images
SOURCE:
American Heart Association
STM Daily News is a vibrant news blog dedicated to sharing the brighter side of human experiences. Emphasizing positive, uplifting stories, the site focuses on delivering inspiring, informative, and well-researched content. With a commitment to accurate, fair, and responsible journalism, STM Daily News aims to foster a community of readers passionate about positive change and engaged in meaningful conversations. Join the movement and explore stories that celebrate the positive impacts shaping our world.
Author
Discover more from Daily News
Subscribe to get the latest posts sent to your email.
Lifestyle
Get chronic UTIs? Future treatments may add more bacteria to your bladder to beat back harmful microbes
Researchers developed a biomaterial releasing beneficial E. coli to combat urinary tract infections by outcompeting harmful bacteria, aiming to reduce antibiotic resistance and manage chronic UTIs effectively.
Sarguru Subash, Texas A&M University
Millions of people in the U.S. and around the world suffer from urinary tract infections every year. Some groups are especially prone to chronic UTIs, including women, older adults and some veterans.
These infections are typically treated with antibiotics, but overusing these drugs can make the microbes they target become resistant and reduce the medicines’ effectiveness.
To solve this problem of chronic UTIs and antibiotic resistance, we combined our expertise in microbiology and engineering to create a living material that houses a specific strain of beneficial E. coli. Our research shows that the “good” bacteria released from this biomaterial can compete with “bad” bacteria for nutrients and win, dramatically reducing the number of disease-causing microbes.
With further development, we believe this technique could help manage recurring UTIs that do not respond to antibiotics.
Bringing bacteria to the bladder
For the microbes living in people, nutrients are limited their presence varies between different parts of the body. Bacteria have to compete with other microbes and the host to acquire essential nutrients. By taking up available nutrients, beneficial bacteria can stop or slow the growth of harmful bacteria. When harmful bacteria are starved of important nutrients, they aren’t able to reach high enough numbers to cause disease.
Delivering beneficial bacteria to the bladder to prevent UTIs in challenging, though. For one, these helpful bacteria can naturally colonize only in people who are unable to fully empty their bladder, a condition called urinary retention. Even among these patients, how long these bacteria can colonize their bladders varies widely.
Current methods to deliver bacteria to the bladder are invasive and require repeated catheter insertion. Even when bacteria are successfully released into the bladder, urine will flush out these microbes because they cannot stick to the bladder wall.
Biomaterials to treat UTIs
Since beneficial bacteria cannot attach to and survive in the bladder for long, we developed a biomaterial that could slowly release bacteria in the bladder over time.
Our biomaterial is composed of living E. coli embedded in a matrix structure made of gel. It resembles a piece of jelly about 500 times smaller than a drop of water and can release bacteria for up to two weeks in the bladder. By delivering the bacteria via biomaterial, we overcome the need for the bacteria to attach to the bladder to persist in the organ.
We tested our biomaterial by placing it in human urine in petri dishes and exposing it to bacterial pathogens that cause UTIs. Our results showed that when mixed in a 50:50 ratio, the E. coli outcompeted the UTI-causing bacteria by increasing to around 85% of the total population. When we added more E. coli than UTI-causing bacteria, which is what we envision for future development and testing, the proportion of E. coli increased to over 99% of the population, essentially wiping out the UTI-causing bacteria. Moreoever, the biomaterial continued releasing E. coli for up to two weeks in human urine.
Our findings suggest that E.coli could stick around and survive in the bladder for extended periods of time and successfully decrease the growth of many types of bacteria that cause UTIs.
Improving biomaterials
Our findings show that E. coli can not only control harmful bacteria it’s closely related to but also a broad range of disease-causing bacteria in humans and animals. This means scientists might not need to identify different types of beneficial bacteria to control each pathogen – and there are many – that can cause a UTI.
Our team is currently evaluating how effectively our biomaterial can cure UTIs in mice. We are also working to identify the specific nutrients that beneficial and harmful bacteria compete over and what factors may help beneficial bacteria win. We could add these nutrients to our biomaterial to be released or withheld.
This research is still at an early stage, and clinical uses are not in development yet, so if it does reach patients it will be well in the future. We hope that our technology could be refined and applied to control other bacterial infections and some cancers caused by bacteria.
Sarguru Subash, Assistant Professor of Veterinary Pathobiology, Texas A&M University
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.
Discover more from Daily News
Subscribe to get the latest posts sent to your email.
Lifestyle
Does Your Favorite Brand of Dark Chocolate Contain Dangerous Metals?
According to a recent article from Consumer Reports, there are some brands of Dark Chocolate that contain dangerous levels of lead, and cadmium.
Dark Chocolate
According to a recent article from Consumer Reports, there are some brands of Dark Chocolate that contain dangerous levels of lead, and cadmium.
Dark Chocolate has become popular due to studies suggesting that they are rich in antioxidants, which is beneficial to the heart, and it having low sugar properties that positively impact health.
The article, which was posted in mid December, states that 28 popular brands were tested, and that 23 of them contained high levels of the dangerous metals.
For more details, check out the article from Consumer Reports: https://www.consumerreports.org/health/food-safety/lead-and-cadmium-in-dark-chocolate-a8480295550/
STM Daily News is a vibrant news blog dedicated to sharing the brighter side of human experiences. Emphasizing positive, uplifting stories, the site focuses on delivering inspiring, informative, and well-researched content. With a commitment to accurate, fair, and responsible journalism, STM Daily News aims to foster a community of readers passionate about positive change and engaged in meaningful conversations. Join the movement and explore stories that celebrate the positive impacts shaping our world.
Author
Discover more from Daily News
Subscribe to get the latest posts sent to your email.
-
Urbanism1 year agoSignal Hill, California: A Historic Enclave Surrounded by Long Beach
-
News2 years agoDiana Gregory Talks to us about Diana Gregory’s Outreach Services
-
Senior Pickleball Report2 years agoThe Absolute Most Comfortable Pickleball Shoe I’ve Ever Worn!
-
Senior Pickleball Report2 years agoACE PICKLEBALL CLUB TO DEBUT THEIR HIGHLY ANTICIPATED INDOOR PICKLEBALL FRANCHISES IN THE US, IN EARLY 2023
-
STM Blog2 years agoWorld Naked Gardening Day: Celebrating Body Acceptance and Nature
-
Automotive2 years ago2023 Nissan Sentra pricing starts at $19,950
-
Travel2 years agoUnique Experiences at the CitizenM
-
Senior Pickleball Report2 years ago“THE PEOPLE’S CHOICE AWARDS OF PICKLEBALL” – VOTING OPEN