Viral quality controls could halt herpes’ spread

Sept. 13, 2011

Herpesviruses are thrifty reproducers — they only send off their most infectious progeny to invade new cells. Two Cornell virologists recently have discovered how these viruses determine which progeny to release.

herpes simplex virion
Recently enveloped herpes simplex virion in the perinuclear space of an infected cell.

The College of Veterinary Medicine researchers report in the Aug. 23 (108:34) issue I of the Proceedings of the National Academy of Sciences on the mechanisms of this quality-control system, which helps streamline viral reproduction to optimize its spreading.

The virologists identified proteins in the nuclear membranes of infected cells that control which viral products exit. This map could be used to identify new targets for future drugs that would hamper viral reproduction by clogging inspection pathways to trap viruses in the cells they first infect.

“When a herpesvirus hijacks a cell, it turns the nucleus into a viral production factory,” said Joel Baines, the James Law Professor of Virology, who co-authored the study with postdoctoral research associate Kui Yang. “It makes protein shells called capsids, stuffs them with viral DNA and ships them out of the nuclear membrane to infect new cells. But errors in the assembly line leave some capsids empty, without DNA, and shipping these is a waste of resources.”

When capsids bud from the nuclear membrane, they take pieces of it with them, forming protective lipid envelopes that let them move to new cells. Empty capsids can’t reproduce, so the virus only allows capsids with DNA through. How the membrane could determine whether the capsid had DNA or not was a mystery until Yang and Baines mapped its method.

Joel Baines
Joel Baines

“We found clamplike proteins on the surface of herpesvirus capsids that hold them together and keep them from bursting when they’re stuffed full of DNA,” said Baines. “Those with DNA have far more of these than empty capsids. We also found a protein complex living in the host cell’s nuclear membrane that binds to these structural support proteins, selecting DNA-filled capsids to pull through the membrane. Thus the virus releases only its most infectious particles.”

This streamlining process has helped herpesvirus species spread prevalently and permanently across all animal species. Eight of the 25 known viruses in the herpes family regularly infect humans, posing a leading cause of human viral infection.

Once in a body, herpesvirus stays for life. It can flare up at any time, causing symptoms and diseases, ranging from infected sores to brain inflammation, birth defects and cancers of the nose, throat and lymphatic system. Though usually not fatal, herpes can prove dangerous to patients with weak immune systems, such as those with HIV/AIDS or infants who contract HIV/AIDS from their mothers.

Various species of Herpesvirus
Various species of Herpesvirus

There is no cure for herpes, but Baines’ map illustrates a viral reproduction system that can be subverted.

“Take away either component, the capsid’s clamplike proteins or the membrane’s inspector proteins, and nothing escapes the host cell,” said Baines. “This opens the door to developing drugs that could block the interactions between these protein complexes, covering the binding sites to clog the system so that no viral particles get through. This would significantly slow or even stop the virus’s spread between cells. Our lab is now working on even more detailed maps of these proteins’ exact interaction sites that will help drug developers pinpoint precise targets to thwart viral reproduction.”

The research was supported, in part, by the National Institutes of Health.

Carly Hodes ’10 is a communication specialist at the College of Veterinary Medicine.

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Original press release:

Cornell University College of Veterinary Medicine news
http://www.vet.cornell.edu/news/herpes.cfm

Media hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Sept11/HerpesMap.html

MyScience

http://www.myscience.cc/wire/discovery_could_lead_to_ways_to_halt_spread_of_herpesvirus-2011-cornell

Bionity

http://www.bionity.com/en/news/134351/study-uncovers-how-herpesvirus-spreads.html?WT.mc_id=ca0067

MedicalXPress (PhysOrg)

http://medicalxpress.com/news/2011-09-discovery-ways-herpes.html

Electronic Component News

http://www.ecnmag.com/News/Feeds/2011/09/blogs-the-cutting-edge-discovery-could-lead-ways-to-prevent-herpes-spread/

Futurity

http://www.futurity.org/health-medicine/how-to-stop-herpes-from-going-viral/

Herpes Pain Relief

http://www.herpespainrelief.info/4349/cornell-chronicle-study-uncovers-how-herpesvirus-spreads/

Simple physics predicts how guts grow

Growing embryos face a tight squeeze when it’s time to pack internal organs. A new study published in Nature Aug. 4 shows how simple mechanical forces between neighboring types of tissue help organs take shape and grow.

gut
The looped shape of an intact gut tube with its anchoring dorsal mesentery. Separation of the dorsal mesentery causes the gut tube to untangle and form a straight tube, as seen in the surrounding tube.

The work is among the first to uncover how an embryo develops from groups of cells into distinctly shaped organs. Though the research largely focuses on the mid-gut in chicken embryos, the findings are relevant to other vertebrates and the formation of other organs, including the heart. Such insights into how organs form could aid efforts to diagnose and prevent birth defects and diseases.

The research reveals how a vertebrate digestive system — a tube up to five times longer than the frame housing it — fits inside the body by packing itself into an organized bundle of intestinal coils. This formation, the researchers report, hinges on the growth of the dorsal mesentery, a bridge of artery-packed tissue anchoring the gut tube.

Natasza Kurpios
Dr. Natasza Kurpios

“Until now the dorsal mesentery seemed to offer only structural support; no one talked about its possible functions,” said developmental biologist Natasza Kurpios, assistant professor of molecular medicine at Cornell’s College of Veterinary Medicine and a first author with Thierry Savin and Amy Shyer of Harvard, where Kurpios conducted the study before she came to Cornell in 2009. “In adults, it’s a thin piece of tissue suspending the intestines and guiding arteries to them. But in embryos, we found that its properties aid construction by pulling back the gut and forcing it to loop.”

Using tiny surgical scissors Kurpios separated the looping gut tube from the dorsal mesentery.

“The gut instantaneously un-looped into a straight tube and the mesentery contracted like a relaxed rubber band,” said Kurpios. “Clearly the mesentery was under tension and the gut-mesentery connection had exerted tension on both that affected each other’s shape. We measured the organs’ growth rates throughout development and found that the gut tube grows far faster than the mesentery: nearly four-fold in chickens. The gut wants to grow, the slower mesentery holds it back, so the gut loops.”

At Harvard, Savin built a simple physical model using a latex sheet (to act as the mesentery) stitched to a rubber tube (to act as the intestine) to mimic the mechanical forces that create the gut looping. Experimenting with different physical properties in the two materials, Savin and colleagues developed a formula predicting the looping patterns based on the thickness and elasticity of the latex and the radius of the rubber tube.

Kurpios and her colleagues then applied the model to animals, finding that in chickens, quail, zebra finches and mice the model predicted the patterns and properties correctly. “We’ve found a simple physical explanation for what had seemed like a complex biological mystery,” Kurpios said.

By uncovering the basic mechanisms for how organs form, researchers may now begin to understand such developmental deformations as intestinal malrotation — which may cause knotting of tissue that blocks circulation — a birth defect in one in 500 newborns that can lead to death.

With the help of a newly funded grant from the March of Dimes, Kurpios says her Cornell lab is completing new research that identifies a hierarchy of specific genes responsible for gut development. “People have not understood how you can go from groups of cells to the actual shape of organs,” she said. “We are now uncovering that link.”

Dr. Natasza Kurpios
Dr. Natasza Kurpios

Other co-authors include Clifford Tabin and L. Mahadevan, both at Harvard. The research was funded by the National Science Foundation, National Institutes of Health and the MacArthur Foundation.

Carly Hodes is a writer at Cornell’s College of Veterinary Medicine.

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Original press release:

Cornell University College of Veterinary Medicine news

http://www.vet.cornell.edu/news/gut.cfm

Media hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Aug11/GutForm.html

R&D Mag

http://www.rdmag.com/News/Feeds/2011/08/general-sciences-study-ids-mechanism-for-how-gut-forms-and-grows/

My Science

http://www.myscience.us/news/simple_physics_predicts_how_the_gut_forms-2011-cornell

Redorbit

http://www.redorbit.com/news/health/2093116/groundbreaking_research_reveals_clues_to_the_formation_of_hearts_intestines/

EurekAlert

http://www.eurekalert.org/pub_releases/2011-08/cu-grr080911.php

Newswise

http://www.newswise.com/articles/view/579309/?sc=rssn

Futurity

http://www.futurity.org/health-medicine/how-gut-grows-is-simple-physics/

Cornell receives $500,000 to tackle salmonella in tomatoes

tomatoTwo experts from Cornell are teaming up to tackle salmonella contamination in produce, thanks to a $500,000 grant from the Agriculture and Food Research Initiative through the U.S. Department of Agriculture (USDA).

Cornell was one of 24 institutions to receive such grants to reduce food-borne illnesses and deaths from microbial contamination. Craig Altier, a salmonella specialist at the Animal Health Diagnostic Center at Cornell’s College of Veterinary Medicine, will work with Greg Martin, Cornell professor of plant pathology and plant-microbe biology and an expert on tomato disease resistance at the Cornell-affiliated Boyce Thompson Institute for Plant Research, to investigate how salmonella interacts with tomatoes with the hope of finding ways to stop its spread.

“My lab explores how salmonella interacts with animal intestinal tracts,” said Altier, associate professor of population medicine and diagnostic science. “Bacteria are very frugal creatures; they turn genes on and off only when they need to. They only turn on the genes that make animals sick when they know they’re in an animal, and we want to know how this process works in plants. We will look at which bacterial genes turn on when salmonella enters a tomato and try to figure out how to intervene.”

salmonellaUnwittingly sharing our food with unseen organisms sends thousands to the hospital each year. Some 50 million Americans get sick every year after consuming food-poisoning pathogens, according to the U.S. Centers for Disease Control and Prevention, and 3,000 of those cases are fatal. Salmonella bacteria pose the biggest food-borne health threat in the United States. While the quest for cleaner food reduced cases of many food-borne pathogens during the past 15 years, salmonella infections continue to rise.

Altier will grow mutant strains of salmonella in his lab to study how the bacteria affect tomatoes when they lack certain genes. He will take strains to Martin’s lab to test them on tomato plants while Martin studies the plants’ immune responses. After running them through the course of infection, Altier will remove the salmonella from the plants to analyze in his lab.

“A number of recent salmonella outbreaks started with contaminated produce,” said Martin. “My lab studies how the tomato immune system acts against certain bacterial pathogens, and this new project will test whether the plant immune system interferes with salmonella’s ability to survive on leaves and fruits. If it does, we may be able to breed new varieties that suppress salmonella growth, which could have implications for lessening salmonella contamination in many different crop plants.”

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Original Press Release:

College of Veterinary Medicine news

http://www.vet.cornell.edu/news/tomatoes.cfm

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/June11/Salmonella.html

Bionity

http://www.bionity.com/en/news/133272/cornell-receives-500-000-to-tackle-salmonella-in-tomatoes.html

My Science

http://www.myscience.cc/en/wire/cornell_receives_500_000_to_tackle_salmonella_in_tomatoes-2011-cornell

US Ag Net

http://www.usagnet.com/state_headlines/state_story.php?tble=NY2011&ID=560

South Dakota Ag Connection

http://www.southdakotaagconnection.com/story-national.php?Id=1372&yr=2011

Bionity

http://www.bionity.com/en/news/133272/cornell-receives-500-000-to-tackle-salmonella-in-tomatoes.html?WT.mc_id=ca0265

 

New Lyme disease test for horses and dogs will help improve treatment

Bettina WagnerRomping through summer fields seems like a harmless pleasure for dogs, horses and humans alike. But just one bite from the wrong tick can rob an animal of that pastime. The bacteria Borrelia burgdorferi catch rides with certain species of ticks and can cause Lyme disease in animals the ticks bite. Catching the disease early is paramount because it becomes progressively harder to fight as the bacteria conduct guerilla warfare from hiding places in the joints, nervous tissues and organs of their hosts.

A new test for Lyme disease in horses and dogs, developed by researchers at the Animal Health Diagnostic Center (AHDC) at the College of Veterinary Medicine at Cornell, will improve our understanding of the disease and pinpoint time of infection, opening possibilities for earlier intervention and more effective treatment plans.

“We’ve offered Lyme disease testing for years,” said Bettina Wagner, the Harry M. Zweig Associate Professor in Equine Health and lead developer of the test, “but we have recently been able to improve our techniques with the multiplex testing procedure. The new test exceeds its predecessors in accuracy, specificity and analytical sensitivity.”

The multiplex procedure, which can detect three different antibodies produced in response to the bacteria associated with Lyme disease using a single test on the sample, eliminates the need for separate tests. In addition, it requires smaller samples and answers more questions about the disease. Multiplex technology has been used for the last decade, but the AHDC is the first veterinary diagnostic laboratory to use it to test for Lyme disease.

Different kinds of antibodies can be found in the body at different stages of infection. The new test can distinguish and measure these differences, giving more information about the timing of the disease.

The bacteria that cause Lyme disease are particularly difficult to detect, according to Wagner, because after infection they tend to hide where they can’t be found. They bury in the joints of dogs, causing arthritis or lameness. Serious kidney disease has also been associated with Lyme infections in dogs. In humans and horses, they also burrow into the nervous system, in the spine or the brain, causing pain, paralysis or behavioral changes. By the time such clinical signs appear, the bacteria are usually not in circulation anymore.

Horse“Now we can distinguish between infection and vaccination and also between early and chronic infection stages,” Wagner said. “That was not possible before. You were able to say whether an animal was infected, but not when it was infected, or how far the infection had developed.”

The test and information the test provides can help veterinarians make advanced decisions about treatment. After the long treatment period ends, veterinarians usually conduct follow-up testing to see if it was successful.

———-

Cornell Chronicle: June 16, 2011
http://www.vet.cornell.edu/news/lymeassay.cfm

Common parasite uncovers key cause of Crohn’s disease

A single human lymphocyte, a white blood cell that acts as part of the immune system. Intraepithelial lymphocytes, which specialize in patrolling intestinal walls, can cause human Crohn's disease.

Immune systems have their sinister side, especially when they have not learned how hard to fight. Crohn’s disease and other inflammatory bowel diseases inflict more than a million Americans with debilitating pain and digestive unrest because of uncontrolled immune responses in the gut.

How this happens remained a mystery until immunologists at Cornell’s College of Veterinary Medicine caught a key culprit in Crohn’s disease: a cell from our own immune forces. With unconventional help from a common parasite, Eric Denkers, professor of immunology, and research associate Charlotte Egan identified a renegade cell responsible for this largely arcane and increasingly prevalent illness.

“Auto-immune diseases are on the rise in this country but their causes have remained largely unknown,” said Denkers. “It’s possible that these diseases are more common in the West because we’re too clean. Exposure to germs trains immune systems how to respond to threats. Early protection from germs may contribute to the increasing prevalence of immune system overreactions in our population, leading to auto-immune problems like allergies and inflammatory bowel disease.”

Similar symptoms arise when some hosts first face the prevalent protozoan Toxoplasma gondii. Denkers’ lab studies this parasite’s arsenal of host-manipulating powers, but recently they have steered Toxoplasma research in an entirely new direction.

Intestinal wall after Toxoplasma infection and inflammation, compared to undamaged intestinal wall.

“We noticed that the initial intestinal inflammation these parasites can cause looks very similar to what happens during Crohn’s disease,” said Denkers, one of the first to study this connection. “Our lab has started using Toxoplasma to model Crohn’s disease in humans and help us find the pivotal perpetrator, which has turned out to be a cell from our own immune forces.”

Specialized immune cells called intraepithelial lymphocytes patrol intestinal walls. Upon encountering invaders, they release messenger proteins that call more immune cells to the battleground. “Too many messenger proteins recruit too many immune cells, causing inflammation that can devastate the host’s own tissue,” Denkers explained. “Bad balance between good bacteria, bad bacteria, and immune interactions like inflammation cause Crohn’s disease.”

“For the first time we’ve discovered how infection can turn these immune cells pathogenic, stimulating them to cause disease, inflammation and necrosis in the small intestine,” said Denkers. “This marks a major leap toward understanding human Crohn’s disease. Unveiling this kind of immunological interplay may lead to improved prevention and care in an array of auto-immune diseases.”

Denkers and colleagues published their discovery in Mucosal Immunology, followed by a review article discussing Toxoplasma infection as a model for Crohn’s disease in the Journal of Biomedicine and Biotechnology in 2010.

~

Cornell Chronicle, February 22, 2011
http://www.news.cornell.edu/…

Scientific Computing, February 23, 2011
http://www.scientificcomputing.com/…

PhysOrg
http://www.physorg.com/…

R&D Magazine
http://www.rdmag.com/…

myScience
http://www.myscience.us/…

Press Connects
http://www.pressconnects.com/

The Ithaca Journal
http://www.theithacajournal.com/

Lifetime achievement award for contributions to poultry health

SchatTwin passions for veterinary research and international development work propelled Dr. Karel “Ton” Schat through a far-reaching career in avian virology and immunology. This past October, friends and colleagues surprised Schat with a unique award at the 5th International Workshop on the Molecular Pathogenesis of Marek’s Disease Virus in Athens, Georgia.

The plaque reads: “in recognition of outstanding research and contributions to poultry health,” commemorating contributions that have spanned flocks and nations around the world and summarizing the adventures and discoveries that have shaped Schat’s career.

“This award is a fitting capstone to Ton’s scientific career,” said Dr. Avery August, chair of the Department of Microbiology and Immunology to which Schat belongs after 32 years of teaching and research at the College of Veterinary Medicine. “I believe that it illustrates the esteem with which his colleagues view him and his work in avian health research, particular his work on Marek’s disease. The department is very proud to have someone of this caliber amongst our faculty.”

A dual degree professor, Schat earned his DVM from the State University in Utrecht, Holland, in 1972, and spent several years exercising his enthusiasm for health research and international development work before earning his PHD from Cornell in 1978. “I knew I wanted to do projects in international development before going on to graduate school,” Schat said, “so during my final year in veterinary school I got a fellowship to spend five months in northern Nigeria researching bacteriological causes of infertility in Fulani cattle. I really enjoyed the work and interacting with the people.”

The experience fueled his international interests, which brought him to Mexico where he met the man who would launch the rest of his career. “The Dutch government hired me to help set up a laboratory in Mexico, researching Marek’s disease,” recalled Schat. “I took six weeks of Spanish and spent a few months learning how to culture cells and grow viruses. Then off I went.”

awardSchat helped get a new laboratory off the ground, trained Mexican counterparts in basic research skills, and conducted his own research on Marek’s disease in chickens. While working in Mexico, Schat met his future mentor, Dr. Bruce Calnek, an eminent poultry professor at Cornell studying Marek’s disease. “He invited me to join his lab at Cornell as a graduate student. When my job in Mexico ended, I came here and I’ve been based here every since,” said Schat.

Early in his graduate career, Schat met Dr. Randy Cole, who had a flock of 28-week-old chickens in full production and free of Marek’s disease on Game Farm Road near campus. Schat took blood samples from the birds and discovered within them a new type of Marek’s disease virus. He used this to develop the SB-1 vaccine for Marek’s disease, dubbed by Schat himself. The widespread vaccine continues to prevent disease in countless chickens, ensuring the health of poultry and its consumers.

After making his mark on Marek’s disease, Schat has continued avian virology research to this day as faculty in the College of Veterinary Medicine Department of Microbiology and Immunology and unit director for avian facilities and research. He has maintained a focus in avian virology, and more recently in chicken infectious anemia virus. In 2006 Schat began making annual pilgrimages to Australia to study the pathogenesis of avian influenza virus in a specialized high-containment disease center. There he works with a mutated strain of the virus taken from an infected human, in research that could have a direct impact on human health.

Schat has attended every one of the eight Marek’s disease symposia that have occurred since they began in 1978 and played important roles in orchestrating several of them. He has attended each of the five workshops for the molecular pathogenesis of Marek’s disease since they began in 2005, and the last such workshop gave him a surprise. “They asked me to present a paper for this meeting, so I arranged to fly down for the fifth time, expecting to give a talk. The award presentation came as a complete surprise. I have worked with and befriended many of the people who come to these meetings and work on these issues, and it was an honor to be recognized by them.”
Schat
The lifetime achievement award joins four other awards given to Schat for his work in poultry health. He and fellow College faculty Dr. Doug Antczak won the first-ever Beecham Award for Research Excellence in 1986, a prestigious award for young investigators in their first six years after post-doc work. That year proved particularly fruitful for Schat, who also won the Upjohn Achievement Award for distinguished contributions in avian medicine.

The year after, Schat received another, particularly meaningful award, the Bart Rispens Research Award in recognition of an outstanding research contribution in the field of avian pathology, from the World Veterinary Poultry Association. It was named after Dr. Bart Rispens, who first taught Schat about Marek’s disease and how to culture viruses. Schat became chair of the award committee the following year.

He later received the Pfizer Award for Excellence in Poultry Research at the 136th Annual Convention of the AVMA in New Orleans, July 1999, and the Merck Award for Achievement in Poultry Science at the 98th Annual meeting of the Poultry Science Association in Auburn, August 2005. The fifth and latest in this series of awards “in recognition of outstanding research and contributions to poultry health” honors Schat’s legacy of accomplishments in his field.


http://www.worldpoultry.net/…
World Poultry News, January 18, 2011

http://poultryproductionnews.blogspot.com/…
Poultry Production News, January 21, 2011