. Scientific Frontline: Virology
Showing posts with label Virology. Show all posts
Showing posts with label Virology. Show all posts

Wednesday, May 17, 2023

New study explains how a common virus can cause multiple sclerosis

Olivia Thomas and Mattias Bronge
Photo Credit: Erik Holmgren

Researchers at Karolinska Institutet have found further evidence for how the Epstein-Barr virus can trigger multiple sclerosis or drive disease progression. A study published in Science Advances shows that some individuals have antibodies against the virus that mistakenly attacks a protein in the brain and spinal cord.

The Epstein-Barr virus (EBV) infects most people early in life and then remains in the body, usually without causing symptoms. The link between EBV and the neurological disease multiple sclerosis (MS) was discovered many years ago and has puzzled researchers ever since. Increasing evidence, including two papers published in Science and Nature last year, suggests that EBV infection precedes MS and that antibodies against the virus may be involved. However, the molecular mechanisms seem to vary between patients and remain largely unknown.

“MS is an incredibly complex disease, but our study provides an important piece in the puzzle and could explain why some people develop the disease,” says Olivia Thomas, postdoctoral researcher at the Department of Clinical Neuroscience, Karolinska Institutet and shared first author of the paper. “We have discovered that certain antibodies against the Epstein-Barr virus, which would normally fight the infection, can mistakenly target the brain and spinal cord and cause damage.”

Tuesday, May 16, 2023

Monkeypox viruses relatively stable on surfaces

Cleaning surfaces with alcohol-based disinfectant is a good protection against infection.
Photo Credit: © RUB, Marquard

The virus remains infectious on steel surfaces for up to 30 days, but can be effectively deactivated by alcoholic disinfectants.

Pockenviruses are known to remain infectious in the area for a very long time. A study by the Molecular and Medical Virology Department at the Ruhr University Bochum showed that the temperature is very important: at room temperature, it can take up to eleven days until there is no longer a reproductive monkeypox virus on a stainless-steel surface, at four degrees Celsius even up to a month. Accordingly, it is particularly important to disinfect surfaces. According to the study, alcoholic disinfectants work well against monkeypox viruses. However, hydrogen peroxide-based disinfectants are not sufficiently effective. The team reports in Journal of infectious diseases.

Weekly observation

Since 2022, the monkey pox virus has been spreading from person to person. Even if the infection is primarily due to direct physical contact, it is possible to infect yourself via contaminated surfaces, for example in the household or in hospital rooms. "Pockenviren is known to remain infectious in the area for a very long time," explains Dr. Toni Meister from the Department of Molecular and Medical Virology at Ruhr University. “So far we have not known the exact times for monkey pox."

Monday, May 15, 2023

Phage structure captured for the first time, to benefit biotech applications

Phage image
Image Credit: Dr Vicki Gold et al, Nature Communications

New insights into the structure of phages will enable researchers to develop new uses for viruses in biotechnology.

Phages are viruses that infect bacteria, which enables them to be exploited as tools in biotechnology and medicine. Now, for the first time, researchers at the University of Exeter, in collaboration with Massey University and Nanophage Technologies, New Zealand, have mapped out what a commonly-used form of phage looks like, which will help researchers design better uses in future.

One common use for phage is phage display, which is a useful tool in drug discovery. Phage display works by linking a gene fragment of interest to a phage gene that makes one of the phage coat proteins. The new coat protein with the linked protein of interest appears on the surface of the phage, where it can be assayed and tested for biological activity.

Billions of types of phages exist. Phage display often uses a type of phage known as filamentous, so called because they are long and thin, making the display of many proteins across its surface possible. Although phage display and other applications have proved successful, until now, scientists have not known what this type of phage looks like.

Gene-edited calf may reduce reliance on antimicrobials against cattle disease

 Brian Vander Ley, associate professor in the University of Nebraska–Lincoln’s School of Veterinary Medicine and Biomedical Sciences, works with Ginger, a Gir cow gene-edited with resistance to bovine viral diarrhea virus.
Photo Credit: Craig Chandler | University Communication and Marketing

Cattle worldwide face major health threats from a highly infectious viral disease that decades of vaccinations and other precautions have failed to contain. Federal, private-sector and Husker scientists are collaborating on a new line of defense, by producing a gene-edited calf resistant to the virus.

If follow-up research confirms its efficacy, the gene-editing approach offers long-term potential to reduce antimicrobial and antibiotic use in the cattle industry.

The bovine viral diarrhea virus devastates the bovine immune system and can cause severe respiratory and intestinal harm to infected beef and dairy cattle, said veterinary epidemiologist Brian Vander Ley, an associate professor in the University of Nebraska–Lincoln’s School of Veterinary Medicine and Biomedical Sciences.

In utero calves are especially vulnerable to infection. If they survive, they can remain infected for life, repeatedly spreading the virus to other cattle.

“They show up as normal cattle but really, they’re shedding a tremendous amount of virus. They’re the ‘Typhoid Marys’ of BVDV spread,” said Vander Ley, assistant director of UNL’s Great Plains Veterinary Educational Center in Clay Center.

Thursday, May 11, 2023

A multiomics approach provides insights into flu severity

Photo Credit: Andrea Piacquadio

Have you ever wondered why some people might get sicker than others, even when they catch the same virus? It is not yet clear why this is. Viral factors (such as differences in the strain of a virus) play a role in this variability, but they cannot account for the wide range of responses in different individuals infected by the same virus. A number of host factors have also been considered, including pre-existing immunity, age, sex, weight, and the microbiome.

Another important factor is the molecular biology within your cells. DNA is shown as one long double-helical strand. So, you might expect that the cell would always read genetic information in order, starting at one end and going to the other. But this isn’t the case. DNA contains transposable elements, sometimes called “junk DNA,” which can change the regions of the genome that are being read at a given time.

The work published in Cell Genomics by an international team led by Dr. Guillaume Bourque, who studied the role of these transposable elements on the severity of illness after influenza A virus infection.

Ancestral mitoviruses discovered in mycorrhizal fungi

Arbuscular mycorrhizal (AM) fungi in the Glomeromycotina colonize plant roots (left, micrograph) and deliver water and nutrients from soil (right).
Image Credit: Tatsuhiro Ezawa

A new group of mitochondrial viruses confined to the arbuscular mycorrhizal fungi Glomeromycotina may represent an ancestral lineage of mitoviruses.

Mitochondria are organelles in the cells of almost all eukaryotes — organisms with cells that have a nucleus. They were originally free-living bacteria capable of generating energy in the presence of oxygen; then engulfed by an ancestral eukaryotic cell where they became mitochondria, the site of cellular respiration and many important metabolic processes. In humans, dysfunctions of mitochondria are associated with aging and many diseases.

Bacteriophages are viruses that infect bacteria. As former bacteria, there are also viruses that infect mitochondria, known as mitoviruses, which evolved from bacteriophages. While mitoviruses have been found in fungi, plants, and invertebrates, they are not well studied.

Associate Professor Tatsuhiro Ezawa at Hokkaido University, Professor Luisa Lanfranco at University of Torino, and Dr. Massimo Turina at National Research Council of Italy (CNR) Torino led an international team to discover a new group of mitoviruses, called large duamitoviruses. Their findings were published in the journal mBio.

Monday, May 8, 2023

Study sheds light on how the immune system protects the body

Photo Credit: RDNE Stock project

Researchers explore how patients with a rare and severe immunodeficiency were still able to defend themselves normally against viruses, including COVID-19

The first study of humans with a rare immunodeficiency reveals how the immune system protects the body against pathogens known to cause serious diseases, such as tuberculosis and COVID-19. The research involving McGill University, paves the way for new therapies to treat autoimmune diseases, chronic inflammatory diseases, and new approaches to vaccine development.

The immune system responds differently to various types of pathogens, like bacteria, parasites, and viruses. However, scientists are still trying to uncover how this complex network functions together and the processes that can go wrong with immunodeficiencies.

“The immune system plays a vital role in protecting the body from harmful germs that make people ill. It’s made up of a complex network of organs, cells, and proteins – like IRF1 or regulatory factor 1, which is key in the regulation of an early immune response to pathogens,” says co-author of the study David Langlais, an Assistant Professor in the Departments of Human Genetics and Microbiology and Immunology at McGill University.

Sunday, April 30, 2023

Scientists Identify Antivirals that Could Combat Emerging Infectious Diseases

Aedes aegypti mosquito.
Photo Credit: Pixabay

A new study has identified potential broad-spectrum antiviral agents that can target multiple families of RNA viruses that continue to pose a significant threat for future pandemics. The study, led by Gustavo Garcia Jr. in the UCLA Department of Molecular and Medical Pharmacology, tested a library of innate immune agonists that work by targeting pathogen recognition receptors, and found several agents that showed promise, including one that exhibited potent antiviral activity against members of RNA viral families.

The ongoing SARS-CoV-2 pandemic, which has claimed nearly seven million lives globally since it began, has revealed the vulnerabilities of human society to a large-scale outbreak from emerging pathogens. While accurately predicting what will trigger the next pandemic, the authors say recent epidemics as well as global climate change and the continuously evolving nature of the RNA genome indicate that arboviruses, viruses spread by arthropods such as mosquitoes, are prime candidates. These include such as Chikungunya virus (CHIKV), Dengue virus, West Nile virus and Zika virus. The researchers write: “Given their already-demonstrated epidemic potential, finding effective broad-spectrum treatments against these viruses is of the utmost importance as they become potential agents for pandemics.”

In their new study, published in Cell Reports Medicine, researchers found that several antivirals inhibited these arboviruses to varying degrees. “The most potent and broad-spectrum antiviral agents identified in the study were cyclic dinucleotide (CDN) STING agonists, which also hold promise in triggering an immune defense against cancer,” said senior author Vaithi Arumugaswami, Associate Professor in the UCLA Department of Molecular and Medical Pharmacology and a member of the California NanoSystems Institute.

Wednesday, April 26, 2023

A 'cocktail' of human antibodies shows promise in fighting severe SARS-CoV-2 infections

Antibody 2A10 (yellow shades) and antibody 1H2 (blue shades) were isolated from a vaccinated research volunteer. The LJI team found these two antibodies can neutralize many SARS-CoV-2 variants.
Illustration Credit: Saphire Lab, La Jolla Institute for Immunology.

An anonymous San Diego resident has become a fascinating example of how the human immune system fights SARS-CoV-2. In a new investigation, scientists from La Jolla Institute for Immunology (LJI) have shown how antibodies, collected from this clinical study volunteer, bind to the SARS-CoV-2 “Spike” protein to neutralize the virus.

Although studies have shown antibodies bound to Spike before, this new research reveals how the original Moderna SARS-CoV-2 vaccine could prompt the body to produce antibodies against the later Omicron variants of SARS-CoV-2. The researchers also captured highly detailed, 3D structures of three promising neutralizing antibodies bound to Spike.

This important work shows exactly where Spike is vulnerable to human antibodies—and how future vaccines and antibody therapeutics might exploit these weaknesses. In fact, studies in mice suggest some of these antibodies may help prevent severe cases of COVID-19.

“To blunt the next pandemic and protect people from seasonal re-emergence of this one, we need antibodies of the broadest possible capacity—ones that are not escaped,” says LJI President and CEO Erica Ollmann Saphire, Ph.D., senior author of the new Cell Reports study. “We found those in a vaccinated San Diegan.”

Thursday, April 20, 2023

Discovery identifies those likely to experience life-threatening dengue fever

(L-R) Co-first author and PhD student Stephanie Studniberg with senior researcher, Monash BDI’s Professor Diana Hansen.
Photo Credit: WEHI

Scientists have discovered cell populations in blood which clearly indicate whether a person infected with dengue fever is likely to progress to life-threatening severe disease or not.

About half of the world’s population is at risk of dengue fever, with almost 400 million annual cases. More will be at risk as global warming enables the spread of mosquito strains that carry the virus.

Until now, there has been no accurate way to predict which patients will progress to severe dengue fever. The new finding uses immune cells to grade potential severity, paving the way for improved patient management, health system savings, and the development of a biomarker test.

Published in the Journal of Biomedical Science, the international research team, led by Professor Diana Hansen at the Monash Biomedicine Discovery Institute, included WEHI in Melbourne, and Dr Tedjo Sasmono at the Eijkman Centre in Jakarta, Indonesia.

Tuesday, April 18, 2023

Durable, low-cost COVID-19 vaccine could help fill in gaps around the world

A protein-based COVID-19 vaccine developed by researchers at Stanford Medicine and their colleagues may be ideal for infants.
Image Credit: Gerd Altmann

In a study led by Stanford Medicine researchers, a low-cost COVID-19 vaccine that does not require refrigeration provided immunity in rhesus monkeys for one year.

A low-cost, protein-based COVID-19 vaccine tested in rhesus monkeys by Stanford Medicine researchers and colleagues offered immunity against known variants for at least one year. Researchers hope the vaccine, which can remain unrefrigerated for up to two weeks and may be especially beneficial for infants, will help alleviate the need for boosters while improving herd immunity around the world.

If the vaccine succeeds in human trials, it could be an alternative to the mRNA vaccines widely used for COVID-19, without drawbacks such as high expense and low-temperature storage requirements. Protein-based vaccines, which use protein fragments of the target virus rather than the whole virus, have been used for decades to protect against diseases such as shingles and hepatitis.

“Our motivation was to come up with a vaccine that would provide worldwide access to vaccination,” said Peter Kim, PhD, the Virginia and D.K. Ludwig Professor in Biochemistry. “In the case of the mRNA vaccines, for example, they are expensive, difficult to make and require storage in freezers. So, we wanted to solve those problems with this vaccine.”

Monday, April 17, 2023

Protein domain common to plants and animals plays role in COVID-19 infection

ORNL scientists mutated amino acids in a receptor protein, shown in green, which diminished interaction with the SARS-CoV-2 virus spike protein, shown in red. Mutating the receptor protein hampered the virus’s ability to infect host cells.
Image Credit: ORNL, U.S. Dept. of Energy

Oak Ridge National Laboratory scientists exploring bioenergy plant genetics have made a surprising discovery: a protein domain that could lead to new COVID-19 treatments.

Researchers found the same plasminogen-apple-nematode, or PAN, domain studied by ORNL in plants like poplar and willow is also present in the human NRP1 receptor protein. NRP1 is less studied than the ACE-2 receptor targeted by current COVID-19 treatments, but this research shows its promise as a future therapeutic target.

By mutating amino acids called cysteine residues in the PAN domain of NRP1, researchers disrupted the ability of the SARS-CoV-2 virus to use its spike protein to invade cells, as described in iScience. ORNL scientists have also linked PAN to the growth of cancerous tumors.

Thursday, March 30, 2023

Lab-made antibodies offer potential cure for yellow fever

Captured through a microscope, this enlarged image illustrates how yellow fever virus (purple coloring) is below detectable levels in the blood of research animals given a monoclonal antibody after being exposed to the virus (bottom squares). By comparison, yellow fever virus is clearly visible in the blood of research animals that didn’t receive a monoclonal antibody (top squares). This research suggests lab-made antibodies may be able to cure people who get sick with yellow fever, a disease for which there is no approved treatment.
Image Credit: Oregon Health & Science University

New research from Oregon Health & Science University and collaborators indicates lab-made antibodies may be able to cure people infected with yellow fever, a virus for which there is no treatment.

The natural immune response to invading pathogens normally involves making protective proteins called antibodies. A study published in Science Translational Medicine suggests that a single monoclonal antibody infusion can strengthen the body’s fight against yellow fever.

In the study, the yellow fever virus was undetectable in all animals that received monoclonal antibody infusions after being exposed to the virus.

“Two monoclonal antibodies that we evaluated completely removed all signs of infection from research animals,” said the study’s corresponding author, Ben Burwitz, Ph.D., associate professor at OHSU’s Vaccine and Gene Therapy Institute and affiliate associate professor at OHSU’s Oregon National Primate Research Center.

Wednesday, March 29, 2023

ORNL-led team designs molecule to disrupt SARS-CoV-2 infection

Oak Ridge National Laboratory led a team of scientists to design a molecule that disrupts the infection mechanism of the SARS-CoV-2 coronavirus and could be used to develop new treatments for COVID-19 and future virus outbreaks.
Video Credit: Michelle Lehman/ORNL, U.S. Dept. of Energy

A team of scientists led by the Department of Energy’s Oak Ridge National Laboratory designed a molecule that disrupts the infection mechanism of the SARS-CoV-2 coronavirus and could be used to develop new treatments for COVID-19 and other viral diseases.

The molecule targets a lesser-studied enzyme in COVID-19 research, PLpro, that helps the coronavirus multiply and hampers the host body’s immune response. The molecule, called a covalent inhibitor, is effective as an antiviral treatment because it forms a strong chemical bond with its intended protein target.

“We’re attacking the virus from a different front, which is a good strategy in infectious disease research,” said Jerry Parks, who led the project and leads the Molecular Biophysics group at ORNL.

The research, detailed in Nature Communications, turned a previously identified noncovalent inhibitor of PLpro into a covalent one with higher potency, Parks said. Using mammalian cells, the team showed that the inhibitor molecule limits replication of the original SARS-CoV-2 virus strain as well as the Delta and Omicron variants.

Coronavirus causes chaos in infected cells’ RNA

Illustration Credit: Fusion Medical Animation

Coronavirus disease (COVID-19) hijacks parts of infected cells' vital RNA machinery, thereby blocking important functions in the cells. These damaging changes in the RNA can likely be reversed, potentially leading to new drugs against COVID-19, University of Gothenburg researchers show.

Genetic material in the body's cells consists of DNA, which serves as long-term storage of genetic information. RNA carries this encoded information to the cells for transcription and translation. These processes enable them to make proteins, which perform most intracellular tasks. The cells' RNA is modifiable to allow correct transfer of the DNA information to the proteins. In recent years, scientific understanding of the complexity and importance of these RNA modifications has grown.

Drastic impact

It has been shown that RNA modifications take place in various viruses, but exactly how the viruses affect the RNA modification processes when they infect cells is unknown. This study reports that SARS-CoV-2 infection disrupts the RNA modifications, and the extent of these RNA modification changes surprised the researchers.

One of the modifications affected by SARS-CoV-2, known as m6A (a multifaceted regulator of gene expression), is highly important for RNA’s basic functions, including transportation of data to the protein-making parts of the cell, and transcription and translation into amino acids there.

“We were surprised at the extent and drastic scale of m6A RNA modification loss in SARS-CoV-2 infection. We also found that the coronavirus variants have differing effects on m6A levels,” says Tanmoy Mondal, researcher at Sahlgrenska Academy, University of Gothenburg, who led the project.

Monday, March 27, 2023

HIV can persist for years in myeloid cells of people on antiretroviral therapy

HIV, the AIDS virus (yellow), infecting a human cell
Image Credit: National Cancer Institute

NIH-funded study confirms white blood cell subtype as HIV reservoir, suggests new target for cure efforts.

A subset of white blood cells, known as myeloid cells, can harbor HIV in people who have been virally suppressed for years on antiretroviral therapy, according to findings from a small study supported by the National Institutes of Health. In the study, researchers used a new quantitative method to show that HIV in specific myeloid cells—short-lived monocytes and longer-lived monocyte-derived macrophages—can be reactivated and infect new cells. The findings, published in Nature Microbiology, suggest that myeloid cells contribute to a long-lived HIV reservoir, making these cells an important but overlooked target in efforts to eradicate HIV.

“Our findings challenge the prevailing narrative that monocytes are too short-lived to be important in cure efforts,” said study author Rebecca Veenhuis, Ph.D., an assistant professor of molecular and comparative pathobiology and of neurology at Johns Hopkins University School of Medicine, Baltimore. “Yes, the cells are short-lived, but our follow-up data show that HIV can persist in monocytes over several years in people who are virally suppressed. The fact that we can detect HIV in these cells over such a long period suggests something is keeping the myeloid reservoir going.”

Thursday, March 23, 2023

Wastewater could be the key to tracking more viruses than just COVID-19

Boehm lab graduate student Winnie Zambrana showing how wastewater samples are processed to test for evidence of viruses.
Photo Credit: Harry Gregory

Researchers have developed methods for using wastewater to track the levels of various respiratory viruses in a population. This can provide real-time information about virus circulation in a community.

Public health experts commonly track spikes in flu, respiratory syncytial virus (RSV), and rhinovirus circulating in a population through weekly reports from sentinel laboratories. These laboratories process samples from only severely ill patients, and it can take weeks for the results to get into the database. Now, for the first time, researchers at Stanford University, in collaboration with Emory University and Verily Life Sciences, have collected fast and accurate readings of a whole suite of respiratory viruses in their local Santa Clara sewer system.

Wastewater is currently the only source for accurate information about COVID-19 rates in communities. PCR testing is no longer widely available, and most people swab themselves at home where their results never reach public health agencies.

Prior to COVID-19, respiratory viruses had not been tracked through wastewater. Most of the viruses the scientists tested for in this study had never been measured in wastewater before. The findings are published in the March 22 issue of The Lancet Microbe.

Tuesday, March 21, 2023

Researchers develop a universal oral COVID-19 vaccine that prevents severe illness in hamsters

Illustration Credit: PIRO

A UCLA-led team has developed an inexpensive, universal oral COVID-19 vaccine that prevented severe respiratory illness and weight loss when tested in hamsters, which are naturally susceptible to SARS-CoV-2. It proved as effective as vaccines administered by injection or intranasally in the research.

If ultimately approved for human use, it could be a weapon against all COVID-19 variants and boost uptake, particularly in low- and middle-income countries, and among those with an aversion to needles.

The study is published in the peer-reviewed journal Microbiology Spectrum.

The oral vaccine is based primarily on the nucleocapsid protein, which is the most abundantly expressed of the virus’s four major structural proteins and evolves at a much slower rate than the frequently mutating spike protein. The vaccine utilizes a highly weakened bacterium to produce the nucleocapsid protein in infected cells as well as the membrane protein, which is another highly abundant viral structural protein.

Monday, March 20, 2023

Lack of canine COVID-19 data fuels persisting concerns over dog-human interactions

A research literature review by Purdue University researchers published in the journal Animals highlights unanswered questions about the COVID-19 virus dynamics between dogs and humans.
 Photo Credit: Purdue Agricultural Communications photo/Tom Campbell

Early COVID-19 pandemic suspicions about dogs’ resistance to the disease have given way to a long-haul clinical data gap as new variants of the virus have emerged.

“It is not confirmed that the virus can be transmitted from one dog to another dog or from dogs to humans,” said veterinarian Mohamed Kamel, a postdoctoral fellow at Purdue University.

During the pandemic’s early days, dogs seemed resistant to the coronavirus, showing little evidence of infection or transmission, said Mohit Verma, assistant professor of agricultural and biological engineering and Purdue’s Weldon School of Biomedical Engineering. “As the virus evolved, or maybe the surveillance technology advanced, there seem to be more instances of potentially asymptomatic dogs.”

These are among the findings that Kamel, Verma and two co-authors summarized in a research literature review “Interactions Between Humans and Dogs in the COVID-19 Pandemic.” The summary, with recent updates and future perspectives, recently appeared in a special issue of the journal Animals on Susceptibility of Animals to SARS-CoV-2.

Underactive immune response may explain obesity link to COVID-19 severity

Intensive care unit at Addenbrooke's Hospital 
Photo Credit: Cambridge University Hospitals NHS Foundation Trust

Scientists at the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID) and Wellcome Sanger Institute showed that following SARS-CoV-2 infection, cells in the lining of the lungs, nasal cells, and immune cells in the blood show a blunted inflammatory response in obese patients, producing suboptimal levels of molecules needed to fight the infection.

Since the start of the pandemic, there have been almost 760 million confirmed cases of SARS-CoV-2 infection, with almost 6.9 million deaths. While some people have very mild – or even no – symptoms, others have much more severe symptoms, including acute respiratory distress syndrome requiring ventilator support.

One of the major risk factors for severe COVID-19 is obesity, which is defined as a body mass index (BMI) of over 30. More than 40% of US adults and 28% of adults in England are classed as obese.

While this link has been shown in numerous epidemiological studies, until now, it has not been clear why obesity should increase an individual’s risk of severe COVID-19. One possible explanation was thought to be that obesity is linked to inflammation: studies have shown that people who are obese already have higher levels of key molecules associated with inflammation in their blood. Could an overactive inflammatory response explain the connection?

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