(Press-News.org) (NEW YORK - May 22) - By comparing flu viruses to the virus that causes measles, researchers fine-tuned a tool that may enable faster vaccine design, according to a study led by Mount Sinai researchers and published online this week in the journal Cell Reports.
The study results revolve around viruses, which are designed perfectly by evolution to invade human cells, inject viral genes and use human genetic machinery to make copies of them. In an endless back and forth, human immune cells have evolved to recognize and attack viral surface proteins, and viruses to constantly change their surface proteins to avoid being recognized. Called antigenic drift, these viral genetic changes proceed at different speeds in different viruses, with implications for vaccine design. While one childhood vaccination provides lifetime protection against measles, for instance, people need a different flu shot every year. The field has long known that flu viruses are much "tolerant" of constant change in certain genes than measles, but not why.
The answer may advance the design of vaccines that target parts of flu viruses they cannot afford to change, the so-called "universal" flu vaccines that would provide permanent immunity. Beyond flu, the new study validates a method that may help the field more quickly design vaccines that provide permanent protection when new and deadly viruses emerge.
"Our team used the measles virus to test a tool that offers a new way to measure the resistance of key viral genes, and related proteins, to change," said lead study author Nicholas Heaton, PhD, a post-doctoral fellow in the Department of Microbiology at the Icahn School of Medicine at Mount Sinai. "It's vital to quickly determine the parts of a virus so vital to its survival that it can't randomly change them because they often make the best vaccine components."
The field has long understood that key parts of the gene code for the measles virus remain unchanged over time, while similar genes in flu viruses constantly change, despite the two both being RNA viruses that infect the lungs. Specifically, the new study found that measles is much less able than the flu to survive genetic changes to the viral surface protein hemagglutinin or H. This protein is central to this story because it both enables viruses to latch onto cells and is well known to human immune cells that seek to destroy anything attached to it.
From past analysis, the team knew going that analogous H protein in influenza viruses is very tolerant of mutations, but the new study confirmed that the measles virus is not. Comparing two related viruses, one rigid and one flexible, in terms of evolutionary speed of surface proteins confirmed that influenza H is more open to change. The researchers reached this conclusion using a high-speed experimental technique, insertional mutagenesis, which changes all of the genes in a virus in one experiment--a useful tool to understand the future of viral evolution. They inserted mutations across the measles genome and found measles cannot survive too much change to the gene for its HA protein especially.
All a flu virus HA needs to attach to a target cell is to find one of the simple sugar structures that cover human cell surfaces. According to a theory supported by the current study results, this simple sugar may be better suited to binding a wider variety of viral HA structures, which may account for the ability of flu H genes to constantly change without consequence. Measles HA and related proteins require a specifically shaped protein receptor to attach to, which may explain why the genes for that protein, and related protein shapes, cannot change and still work.
"In theory, how different viruses evolved to attach to target cells may be a major factor driving their genetic rigidity, or flexibility, which influences the ability to tolerate the random genetic changes that are happening all the time," said Dr. Heaton. "Both the flu and measles have historically been very successful invaders of human cells, so both rigidity and constant change genetic change have conferred value. Exactly why tradeoffs are made in viral evolution is very interesting, and the subject of ongoing studies."
INFORMATION:
This study was funded by the National Institutes of Health. Along with Dr. Heaton, study authors in the Department of Microbiology were Benjamin Fulton, Shannon Beaty, Sohui Won and Benhur Lee and Peter Palese. The study's second author was David Sachs of Genetics and Genomic Sciences at the Icahn School of Medicine at Mount Sinai.
About the Mount Sinai Health System
The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven member hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community?based facilities to tertiary and quaternary care.
The System includes approximately 6,600 primary and specialty care physicians, 12?minority?owned free?standing ambulatory surgery centers, over 45 ambulatory practices throughout the five boroughs of New York City, Westchester, and Long Island, as well as 31 affiliated community health centers. Physicians are affiliated with the Icahn School of Medicine at Mount Sinai, which is ranked among the top 20 medical schools both in National Institutes of Health funding and by U.S. News & World Report.
Under the direction of the Hertzberg Palliative Care Institute, Mount Sinai is a national leader in providing palliative care services.
For more information, visit http://www.mountsinai.org, or find Mount Sinai on Facebook, Twitter and YouTube.
(PARIS, FRANCE) Technique, talk, and talent were three buzzwords at the 2015 EuroPCR congress. As in years past, the conference featured a mix of breaking news, live case demonstrations, oral and poster sessions, debates, and tips-and-tricks tutorials. New study data have been increasingly showcased at EuroPCR and this year's meeting featured over 70 new abstract sessions throughout the four-day meeting, across five interventional tracks.
One of the focus topics at this year's meeting was a spate of recent trials showing a benefit for mechanical thrombectomy in acute ...
URBANA, Ill. - The widespread evolution of herbicide-resistant weeds is costing farmers, especially through decreases in productivity and profitability. Although researchers and industry personnel have made recommendations to slow this evolution, an understanding of the patterns and causes of the resistance has been limited.
Diversifying the herbicide mechanisms of action (MOAs) has been recommended to stop the spread of herbicide-resistant weeds. MOAs refer to the biochemical interaction that affects or disrupts the target site in the weed. Two common methods of diversifying ...
The first definitive summary of the best and safest blood pressure lowering treatments for kidney disease and diabetes patients has been compiled by New Zealand doctor and researcher Associate Professor Suetonia Palmer.
The international relevance of her work for doctors, patients and those who decide which drugs to fund has been demonstrated by the prestigious Lancet medical journal publishing an article on her study in its latest edition.
The University of Otago, Christchurch, researcher together with a global team used innovative statistical analysis to compare hundreds ...
Berkeley -- Researchers at the University of California, Berkeley, have developed algorithms that enable robots to learn motor tasks through trial and error using a process that more closely approximates the way humans learn, marking a major milestone in the field of artificial intelligence.
They demonstrated their technique, a type of reinforcement learning, by having a robot complete various tasks -- putting a clothes hanger on a rack, assembling a toy plane, screwing a cap on a water bottle, and more -- without pre-programmed details about its surroundings.
"What ...
WASHINGTON, D.C., May 22, 2015 -- Play a flute in Carnegie Hall, and the tone will resonate and fill the space. Play that same flute in the Grand Canyon, and the sound waves will crash against the rock walls, folding back in on each other in sonic chaos. The disparity in acoustics is clear - to the modern listener, the instrument belongs in an auditorium.
"Distinct echoes would be totally unforgivable in today's performance spaces," says Steven J. Waller, an archaeo-acoustician who has studied prehistoric rock art and the acoustics of ancient performance spaces. "But, ...
WASHINGTON, D.C., May 22, 2015 -- The room is loud with chatter. Glasses clink. Soft music, perhaps light jazz or strings, fills the air. Amidst all of these background sounds, it can be difficult to understand what an adjacent person is saying. A depressed individual, brought to this cocktail party by a well-meaning friend, can slide further into himself, his inability to hear and communicate compounding his sense of isolation.
"A lot of research has suggested that these people with elevated depression symptoms have a bias towards negative perception of information ...
Why do good people do bad things? It's a question that has been pondered for centuries, and new research published by the Society for Personality and Social Psychology may offer some insights about when people succumb to versus resist ethical temptations.
"People often think that bad people do bad things and good people do good things, and that unethical behavior just comes down to character," says lead research author Oliver Sheldon, PhD. "But most people behave dishonestly sometimes, and frequently, this may have more to do with the situation and how people ...
Parasitic worms can pose a serious threat to the Dungeness crab, a commercially important fishery species found along the west coast of North America. The worms are thought to have caused or contributed to the crash of the crab fishery of central California during the last half century. New research shows that infected crabs can rid themselves of parasites by moving into the less salty water of estuaries. Low salinity kills the worms creating a parasite refuge for the crabs.
The large Dungeness crab (Metacarcinus magister) is an important source of income for fishermen ...
Ecologists from the University of York, together with the Wildlife Conservation Society (WCS) and the Uganda Wildlife Authority (UWA), have developed a new method to better identify where poachers operate in protected areas.
Published in Conservation Biology, the analysis provides spatial maps of illegal activities within Queen Elizabeth National Park, one of Uganda's most important protected areas for elephant conservation.
Analysing 12 years of ranger-collected data, different types of threats were monitored and recorded, including the commercial hunting of large ...
The German Institute for Quality and Efficiency in Health Care (IQWiG) has assessed documents subsequently submitted by the drug manufacturer in the commenting procedure on the dossier assessment of the fixed-dose drug combination of ledipasvir and sofosbuvir (trade name: Harvoni). According to the findings, a hint of a non-quantifiable added benefit for a further patient group can be derived from this additional information.
This patient group consists of treatment-naive or pretreated patients with hepatitis C virus (HCV) infection of genotype 1 who are also infected ...
