Imagine you’re taking a refreshing night swim in the warm blue waters of Vieques in Puerto Rico. You splash into the surf and head out to some of the deeper waters of the bay, when what to your wondering eyes should appear, but blue streaks of light in water that once was clear. Do you need to get your eyes checked? Are you hallucinating? No! You’ve just happened upon a cluster of dinoflagellates, harmless bioluminescent microorganisms called plankton, that emit their glow when disturbed by movement. These dinoflagellates are known to inhabit waters throughout the world but are generally not present in large enough numbers to be noticed. There are only five ecosystems in the world where these special bioluminescent bays can be seen, and three of them are in Puerto Rico.
Bioluminescent plankton in the ocean
But you don’t have to travel to Puerto Rico or swim with plankton to see bioluminescence. There are bioluminescent organisms all over the world in many unexpected places. There are bioluminescent mushrooms, bioluminescent sea creatures—both large and small (squid, jellyfish, and shrimp, in addition to the dinoflagellates)—and bioluminescent insects, to name a few. Bioluminescence is simply the ability of living things to produce light.
Canine distemper virus (CDV) is a highly contagious pathogen that is the etiological agent responsible for canine distemper (CD), a systemic disease that affects a broad spectrum of both domestic dogs and wild carnivores. While there are commercially available vaccines for CDV that can provide immunity in vivo and protect canines from contracting CD, there is a strong demand for effective canine distemper antivirals to combat outbreaks. Such drugs remain unavailable to date, largely due to the laborious, time-consuming nature of methods traditionally used for high-throughput drug screening of anti-CDV drugs in vitro. In a recent study published in Frontiers in Veterinary Science, researchers demonstrated a new tool for rapid, high-throughput screening of anti-CDV drugs: a NanoLuc® luciferase-tagged CDV.
A recent article published in Cancers demonstrates a new method for targeting glial cells using a lentiviral packaging system that incorporated Zika virus envelope proteins. By using the reporter gene firefly luciferase, researchers demonstrated that a pseudotyped virus could infect cultured glioblastoma cells.
Introduction
Space-fill drawing of the outside of one Zika virus particle, and a cross-section through another as it interacts with a cell. The two main proteins of the viral envelope, the envelope proteins and membrane proteins, are shown in red and purple respectively. The lipid membrane of the envelope is shown in light lavender. The capsid proteins, in orange, are shown interacting with the RNA genome, in yellow, at the center of the virus. The cell-surface receptor proteins are in green, the cytoskeleton in blue, and blood plasma proteins in gold. Drawn and copyright owned by David Goodsell.
Viruses enjoy a fearsome reputation. SARS-CoV-2 is only the latest infectious agent that has garnered attention by becoming a worldwide pandemic. Even the viral name suggests that SARS-CoV-2 was not the first of its type [SARS-CoV is the virus behind the severe acute respiratory syndrome (SARS) that spread worldwide in the early 2000s]. There are many different families of viruses (e.g., coronavirus for SARS-CoV-2 or lentiviruses for HIV-1) and each show a preference to the cell types they want to infect. By investigating the life cycle of viruses to better understand their mechanisms, researchers can discover new opportunities that may be exploited.
In 2015 and 2016, the virus that concerned health authorities was Zika virus (ZIKV). While this virus generally caused mild disease, the babies of women who were infected during pregnancy were at increased risk for microcephaly and other brain defects. These defects were traced back to Zika virus infecting nerve tissue, specifically, glial cells. This discovery provided an opportunity to explore how Zika virus might affect the brain tumor, glioblastoma multiforme (GMB), especially the glioblastoma stem cells (GSCs) that resist conventional treatment and contribute to the poor prognosis for GMB. Studies suggested that Zika virus infection prolonged survival in animal glioma models and selectively killed GSC with minimal effects on normal cells. In fact, the molecules used by ZIKV to enter cells were predominantly found on tumors, not normal cells. Knowing that the ZIKV envelope proteins prM and E provide the target specificity for glial cells, Kretchmer et al. wanted to explore if ZIKV envelope proteins substituted in lentivirus packaging systems would be able to enter glioblastoma cells.
Illustration from CDC; Photo Credit: Alissa Eckert, MS; Dan Higgins, MAM
When you look at our top 10 most viewed blog posts of 2020, there’s no surprise that all relate to COVID-19. We have come a long way since the beginning of the year, thanks to tireless scientists and researchers around the globe. They have led the way in COVID-19 research, treatment, and testing. Let’s take a closer look at this top 10 list:
10. Tips to Maintain Physical Distance in the Lab
The spread of COVID-19 forced us to adapt and adjust to new ways in life, in work, and for this blog post, in the lab. In response to the pandemic, some labs shut down completely. Others have stayed open, especially those involving coronavirus research. This post provides 10 helpful distancing tips for researchers to stay safe and productive while working in the lab.
9. Investigation of Remdesivir as a Possible Treatment for SARS-2-CoV (2019 nCoV)
Scientists have worked hard to determine possible treatment for COVID-19. This blog post focuses on Remdesivir (RDV or GS-5734), an encouraging treatment used for the first case in the United States. It provides an in-depth look at numerous studies and clinical trials on Remdesivir as treatment for COVID-19. One key finding is that RDV needed to be administered either before or shortly after infection to limit lung damage.
Kasia Slipko (middle) and her lab at Vienna University of Technology. She and colleagues are exploring using wastewater to monitor viral disease outbreaks.
When Kasia Slipko started graduate school at Vienna University of Technology, Institute for Water Quality and Resource Management, she was interested in studying antibiotic resistant microbes in wastewater. For three years, she evaluated different wastewater treatment methods to find out how to remove antibiotic resistant bacteria. But in the spring of 2020, her research took an unexpected turn. That was when the COVID-19 global pandemic hit, caused by the rapid spread of the SARS-CoV-2 virus. Kasia soon found herself at the forefront of another exciting field: using wastewater to monitor viral disease outbreaks.
The SARS-CoV-2 nucleocapsid protein accounts for the largest proportion of viral structural proteins and is the most abundant protein in infected cells. Nucleocapsid proteins have the job of “packaging” the viral nucleic acid (in this case, RNA). Viral nucleocapsid proteins can also enter the host nucleus and interact with a variety of host proteins to interfere with critical processes of the host cell, including protein degradation. Here we review a study that used an in vitro protein degradation assay to investigate the interaction of the SARS-CoV-2 nucleocapsid protein and the proteasome activator PA28γ.
In SARS-CoV-2 infections, the nucleocapsid protein is critical for infection, replication and packaging. The SARS-CoV-2 nucleocapsid protein is not only localized in the cytosol of the host cell but also is translocated into the nucleus. There, it interacts with various cellular proteins that modulate cellular functions, such as the degradation of unneeded or damaged proteins by proteolysis. Researchers have proposed that the protein degradation system plays an important part in coronavirus infection (1).
The fall of 2020 was like no other, especially for universities. The COVID-19 pandemic hit most of the world in the spring, forcing schools and businesses to close. For months, people worked from home and schools switched to online classes. When fall came, universities had a difficult decision to make. Do they have students and staff come back to campus for in-person classes? With students living together in close proximity in dormitories, an outbreak could quickly get out of hand. How can the university monitor and control the spread of the virus to ensure everyone’s safety?
This was when Robert Brooks started getting calls. He’s the Technical Director and Operations Manager at Microbac Laboratories in Oak Ridge, Tennessee. Microbac is a network of privately owned laboratories that provide testing services for food products, environmental samples and the life science industry. Robert has been in the lab industry for 25 years and has established a reputation for taking on difficult problems. “We really try to go that extra mile to help clients solve their issues. That has made a name for us out there. When people have odd-ball issues, they give us a call cause we’re going to take a look at it from a couple different viewpoints and take a step-by-step approach,” he says.
Since the COVID-19 pandemic swept the world in early 2020, many scientists in the viral research community have shifted their focus to study the SARS-CoV-2 coronavirus. Dr. Colleen Jonsson is one of them. She’s the Director of the Regional Biocontainment Laboratory, and Director of the Institute for the Study of Host-Pathogen Systems at the University of Tennessee Health Science Center (UTHSC) in Memphis.
Dr. Jonsson has been studying highly pathogenic human viruses for more than three decades. She has led several cross-institutional projects using high-throughput screens to discover small molecule antiviral compounds that could be used as therapeutics. And now, she’s using that experience to find an antiviral therapeutic against SARS-CoV-2.
This post is written by guest blogger, Melanie Dart, PhD, Sr. Research Scientist at Promega.
Melanie Dart, PhD.
Along with lockdowns and sheltering in place efforts, the COVID-19 pandemic brought a unique challenge to our doorstep this spring: developing a clinical serological test for COVID-19 to detect the presence of antibodies against the SARS-CoV-2 virus. The project was one of the fastest, most dynamic development efforts ever undertaken at Promega. In general, in vitro diagnostic (IVD) tests take at least one to two years to develop. Nothing about 2020, however, has been typical.
It was important to move quickly. We set an aggressive timeline, and to meet it we needed not only dedication of our internal team, but also contributions from the local community.
In the Northern hemisphere, the cold and flu season is about to start. Most years that means people schedule flu shots, dust off chicken soup recipes and stock up on tissues. If they start to feel sick, they stay home for a day or two, drink hot tea, eat warm soup and—for the most part— go on with their lives.
This is not, however, most years. This year the world is battling a pandemic virus, SARS-CoV-2. Symptoms of COVID-19, the disease caused by this virus, mirror those of the flu and common cold, and that overlap in symptoms is going to make life more complicated. Most years, a mild cough or minor body aches wouldn’t even warrant a call to the doctor. This year these, and other undiagnosed cold- and flu-like symptoms, won’t be easily ignored. They could mean kids have to stay home from school, and adults have to self-quarantine from work, for up to 2 weeks. In years past people might have been comfortable treating their symptoms at home, this year people will want answers: Is it the flu? Or is it COVID-19?
