Category Archives: Microbiology

First proven ovarian cancer origin could unlock earlier detection in many human cancers

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A very large ovarian cancer as seen on CT

The most common and aggressive type of ovarian cancer, ovarian carcinoma, leaves a dark trail. Science has learned too little and most women learn too late to treat the deadly disease.

Cornell scientists have found ovarian carcinoma’s first proven origin cells and uncovered clues for finding similar sources of other cancers. Published in Nature in March 2013, the study opens paths for new screening methods to detect cancer earlier and increase treatment chances in the ovaries and beyond.

Most organs have stem-cells, which help healing and development, but many cancers start when such cells go astray. Using a novel cell location technique never before used in ovaries, the Cornell study uncovered a nest (niche) of particularly cancer-prone stem cells at an area in the ovaries where different tissue types meet. It provides the most direct proof yet that vulnerable stem cells can nest near such tissue junctions, which occur throughout the body.

“Poor understanding of ovarian cancer’s development has posed the biggest roadblock to helping its victims,” said Dr. Alexander Nikitin, pathology professor at Cornell’s College of Veterinary Medicine and leader of the Cornell Stem Cell Program. “We have found what is very likely to be the source of cells from which ovarian carcinoma arises, as well as the strongest suggestion yet that cancer-prone stem cells can nest in tissue junctions. This could spur new discoveries of cancer-prone stem cell niches throughout the body, revealing new ways to screen for and diagnose several different cancers.”

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Stem cells expressing stem cell marker ALDH1 (red) and retaining proliferation label BrdU (green) in the hilum region of the ovary

A woman’s risk of getting aggressive ovarian cancer in her lifetime is about 1 in 72, according to the American Cancer Society. Once diagnosed, 70% will die within five years. No good screening tests exist, but uncovering a specific location that seeds it could let people catch it earlier and change those chances for the better.

Nikitin’s lab found the new cancer-prone stem cell niche using direct lineage tracing, a new technique that labels and tracks cells. The niche, found near the junction of the ovaries and the uterine tube (also known as the Fallopian tube), houses stem cells that regenerate the ovarian surface epithelium, a cover that opens when females ovulate and must grow back each time.

But Nikitin’s team found that these cells turned cancerous when two important tumor suppressor genes p53 and Rb were deleted. These genes have been shown to be inactive in human ovarian carcinoma. Nikitin’s lab had previously proven that properly functioning p53 and Rb protected against ovarian carcinoma development in the mouse.

The new study showed that newly discovered stem cells without p53 and Rb grew faster and showed more aggressive metastatic behavior compared to more mature cells. Nikitin is now working on leveraging his lab’s discoveries to find cancer-prone stem cells at similar junction areas in human ovaries and other places where two different types of tissue converge, such as the esophagus and stomach, anus and rectum, and different parts of the uterus. Such junctions are breeding grounds for tumors.

“Until now, we have had no explanation for why so many tumors form at junction sites,” said Nikitin. “Our study suggests new undiscovered stem cell niches might occur beyond the ovaries. It’s likely to lead scientists to search for similar cancer-prone stem cell niches at other junctions, which could lead to specific diagnostic screening tests to detect cancers earlier.”

Published 3/7/13

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New Salmonella Dublin test for milk and cattle available for first time in US

Salmonella can cause serious disease on cattle farms, killing calves, causing cows to abort, contaminating raw milk, and harming humans along the way. While the cattle-adapted strain Salmonella Dublin creeps into the Northeastern US, veterinarians and farmers struggle to catch the bacteria in time to protect livestock because these bacteria often hide dormant in carrier animals, making the strain particularly hard to diagnose.

For the first time in the US, a more useful test for Salmonella Dublin is now available exclusively at the Cornell University College of Veterinary Medicine’s Animal Health Diagnostic Center (AHDC). Cheaper, quicker, safer, and more sensitive, the test detects antibodies rather than bacteria. Traditional bacteriological tests could only identify S. Dublin organisms in sick or deceased animals, missing up to 85% of infections in carrier cattle. The new test reveals carriers, helping farmers and veterinarians monitor infection spread over time and track the impact of control measures in ways that were previously impossible.

Dairy-cows-Pavement“We’re very concerned about this disease spreading east because it could severely harm animal and human health, as well as the livelihoods of dairies in the region,” said Dr. Belinda Thompson, senior extension associate at the AHDC. “Salmonella Dublin is already common west of the Mississippi River, but it’s only recently being recognized in the Northeastern US. We want to be pro-active now to keep it out of our farms.”

In recent years the AHDC has dealt with several high-morbidity and high-mortality outbreaks of Salmonella Dublin in New York and other states. To address the problem before it grows further, Dr. Bettina Wagner, director of the Serology and Immunology Section of the AHDC laboratory, secured the nation’s first USDA permit to import and use the enhanced test.

While Salmonella Dublin usually doesn’t make adults cows very sick, it can wreak havoc on young and unborn calves, particularly in populations like those in the East Coast that haven’t been exposed. Its resistance to many common antibiotics severely limits treatment options and, to make matters even worse, it often presents as respiratory disease, throwing off track veterinarians trained to recognize diarrhea as salmonella’s telltale sign.

“Infected calves often look fine the day before a sudden rapid onset, the next day they look depressed, and the next day they die,” said Dr. Paul Virkler, senior extension associate at the AHDC. “Veterinarians often think it’s something else-. We’ve seen newly infected herds in which every single calf in a particular age group dies. We’re trying to keep this from getting to baby calves, the life and future of a farm, and the animals most at risk.”

People working with cattle are also at risk. All Salmonella strains affect most vertebrates and can jump between species. Even carriers that don’t seem sick can shed bacteria, and people, companion animals, and other livestock can pick up the infection through contact with any bodily excretion.

“People have died drinking raw milk with Salmonella Dublin,” said Virkler. “It’s one of the bad players in raw milk. Pasteurizing milk will kill the bacteria.”
Prior to the new test’s release, testing had to be done animal by animal. The new antibody test can use milk samples straight from bulk milk tanks to find whether a herd has been exposed. It can also work with blood samples and diagnose individuals, helping keep unexposed herds infection-free by removing infected animals and pre-screening new animals farmers are considering buying.

“Herd managers can take preventative measures and help control the infection’s spread by isolating sick calves, pasteurizing milk, managing cattle movement, and improving hygiene,” said Thompson. “But to see if any of this is working, they need a tool to monitor success. We didn’t have that until now. This test will let us learn about the prevalence of Salmonella Dublin on the East Coast and hopefully nip it in the bud.”
cows in field

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http://vet.cornell.edu/news/Dublin.cfm

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Oct12/SalmonellaDublin.html

Meat Trade News Daily

http://www.meattradenewsdaily.co.uk/news/291112/usa___a_lack_of_understanding_over_salmonella_.aspx

MyScience

http://www.myscience.us/wire/cornell_offers_only_u_s_salmonella_dublin_test_for_cattle-2012-cornell

The Post Standard: Syracuse.com

http://blog.syracuse.com/farms/2012/11/better_test_for_cattle_disease.html

Phys.org

http://phys.org/news/2012-11-cornell-salmonella-dublin-cattle.html

Drovers CattleNetwork.com

http://www.cattlenetwork.com/cattle-news/Cornell-offers-only-US-salmonella-dublin-test-for-cattle-176821551.html?ref=551

Bovine Veterinarian Online

http://www.bovinevetonline.com/news/industry/Cornell-offers-only-US-salmonella-dublin-test-for-cattle-176821551.html

USAgNet

http://www.usagnet.com/story-national.php?Id=2486&yr=2012

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http://www.dairyherd.com/dairy-news/latest/Cornell-offers-only-US-salmonella-dublin-test-for-cattle-176821551.html

Food Safety News

http://www.foodsafetynews.com/2012/11/cornells-new-test-spots-salmonella-in-cattle/

Ithaca Journal

http://www.theithacajournal.com/article/20121111/NEWS01/311110027/Cornell-test-detects-salmonella-cattle?odyssey=mod|newswell|text|FRONTPAGE|p

Before It’s News

http://beforeitsnews.com/food-and-farming/2012/11/cornells-new-test-spots-salmonella-in-cattle-2446024.html

Healthy Cooking News

http://healthycookingnews.blogspot.com/2012/11/cornells-new-test-spots-salmonella-in.html

Beef Cattle News

http://savant7.com/beefcattlenews/

Stop Foodborne Illness

http://www.stopfoodborneillness.org/content/cornell%E2%80%99s-new-test-spots-salmonella-cattle

MeatingPlace

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CABI.org VetMed Resource

http://www.cabi.org/VetMedBeta/news/22617

The Meat Site

http://www.themeatsite.com/meatnews/19365/cornell-offers-us-salmonella-dublin-test-for-cattle

Surprise packages sent by cancer cells can turn normal cells cancerous

Surprise packages sent by cancer cells can turn normal cells cancerous, but Cornell scientists have found a way to keep their cargo from ever leaving port. Published in Oncogene in January 2012, their study demonstrates the parcels’ cancer-causing powers, describes how they are made, and reveals a way to jam production. Treatments that follow suit could slow tumor growth and metastasis, the spread of cancer to new parts of the body.

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A cancer cell (bottom right) producing and shedding microvesicles, which travel between cells and attach to a normal cell (upper left) to unload cancerous cargo

Remote recruiting through inter-cellular mail lets cancer cells grow their ranks without having to move. While most cells communicate through a standard postal system of growth factors and hormones, cancer cells and stem cells use bulkier parcels called microvesicles. These big packages are stuffed with unconventional cargo that boosts the survival and growth rates of recipient cells and can dramatically alter their behavior and surrounding environment. The cargo of microvesicles includes unique sets of proteins that often reflect their cell of origin and are capable of completely changing a cell’s form and function.

“Stem cells make microvesicles containing one set of proteins that can help heal damaged tissue, while cancer cells make malignant microvesicles called oncosomes that contain another set of proteins which facilitate the growth and spread of tumors,” said Dr. Richard Cerione, professor at the College of Veterinary Medicine and co-author.

Dr. Marc Antonyak and graduate student Bo Li, co-authors and researchers in Cerione’s lab, examined cells in culture to observe the effects of oncosomes on normal cells. They focused on fibroblasts, a normal cell type that is often found associated with human tumors and helps to facilitate tumor growth.
“We incubated healthy fibroblasts together with aggressive breast cancer cells,” said Antonyak. “Although we’d disabled the cancer cells from forming tumors on their own, they kept pumping out oncosomes. The fibroblasts that were bathed in these oncosomes began turning cancer-like, living longer, growing faster, and forming tumors.”

Using a variety of techniques to parse out participating proteins, including immunoblot analysis, immunofluorecence, and electron microscopy imaging, Antonyak identified each link in this pathway and traced it back to the first: a protein called RhoA that acts like a lever initiating microvesicle production. Cancer cells crank production into overdrive, said Antonyak, but jamming the lever could stop the whole assembly line.

“Even if we immobilize cancer cells, as long as they can make these microvesicles they can continue spreading vital components for the development of cancer,” said Cerione. “It’s clear that microvesicles can change the behavior of cells and play an important part in cancer progression. Treatments targeting the microvesicle production pathway we’ve outlined could have a real impact on slowing cancer progression.”

Microvesicles_000 (1)

 

 

 

 

 

 

 

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http://vet.cornell.edu/news/CancerCargo.cfm

 

Ticks untold

Prime suspects in mystery fevers may hold new tick-borne diseases
Suddenly your horse is sick and you don’t know why. She breathes normally but her temperature is rising, her eyes grow yellow with jaundice, she seems depressed, and barely eats. The fever is clear but the cause is not; even the most experienced experts can offer no concrete answers. Eventually the fever fades, but is that the end of whatever caused it or is the source still lurking somewhere inside?

Horse owners across the states are facing this distressing scenario. At the Cornell University Animal Health Diagnostic Center (AHDC), Dr. Linda Mittel fields a growing number of calls about these mysterious fevers of unknown origins (FUOs). Many come from the Northeast, Mid-Atlantic, and Great Lakes areas: the nation’s topmost hotbeds of human tick-borne disease. This pattern led Mittel to suspect that the culprits of the fever caper could be ticks and the difficult-to-diagnose diseases they carry.

“Tick-borne diseases are some of the fastest growing emerging diseases in the United States right now,” said Mittel. “As ticks continue expanding their numbers and geographic range these diseases may affect new areas. We get calls about fevers at broodmare operations, showbarns, and farms where race horses rest or layup, even in areas where they didn’t know they had ticks. But horses moving between states can move ticks with them, and the effects of this movement are starting to show.”

Mittel and colleagues at the AHDC are embarking on a project to find just what diseases ticks in hotbed zones are carrying and whether they are behind the wash of mystery fevers in horses. The study will use samples from horses suffering FUOs to look for bacterial infections known to be transmitted by ticks (Anaplasma, Babesia, Borrelia, Ehrlichia, and Rickettsia) as well as other bacteria known to cause non-respiratory infection in horses (Leptospira, Bartonella, and Neorickettsia.)

These agents are considered emerging infectious diseases in humans, and this will be the first study determining their presence in horses with FUOs. The study will also sample ticks found on or near horses in designated areas to find which pathogens they carry and to potentially discover previously undocumented tick-borne pathogens.

Many tick-borne diseases are sensitive to specific drugs; others are not sensitive to antibiotics at all. Knowing which diseases are at the root of FUOs will help veterinarians treat them effectively. It will also help owners understand how the causes of fevers might impact affected horses’ futures in racing, performance, or showmanship.

“I’m quite excited to start solving the mysteries of these fevers and to possibly uncover new previously unrecognized diseases – in horses and people,” said Mittel. “If these agents are in the horses, humans may also have them without realizing– people who work with these horses might be particularly at risk. Knowing what we’re dealing with here will hopefully solve the mystery of FUOs and help equine and human medicine recognize and address the growing onslaught of tick-borne disease.”

This research is funded by the Harry M. Zweig Memorial Fund for Equine Research.

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First discovery of cells expelling mitochondria uncovers newfound survival tactic

An ancient union between cell and organelle has shown the first sign of fracture, challenging common conceptions of a primordial partnership all multicellular organisms rely on to live. Cornell researchers have recorded the first direct evidence of cells expelling intact mitochondria, the cellular machinery responsible for energy production.

AAAmitochondria B

An illustrated mitochondrion

Malfunctioning mitochondria produce free-radicals that damage cells, contributing to aging, mitochondrial myopathies, and disorders ranging from schizophrenia, bipolar disorder, and dementia to Parkinson’s disease and multiple sclerosis. The newfound breakup behaviour, described in Mitochondrion 2011 Nov.11(6), may be an early cell-survival strategy to escape the toxic effects of damaged mitochondria.

“It is very surprising to see living cells actively jettisoning vital parts of themselves,” said Dr. Theodore Clark, immunologist at the College of Veterinary Medicine. “This is the first time full mitochondria have been found outside cells and it may account for 15 years’ worth of unexplained data showing mitochondrial DNA and protein in extracellular spaces. We think these cells’ behaviour reveals a newfound survival tactic deeply rooted in evolution.”

Today’s mitochondria evolved from freewheeling bacteria that settled down in other cells two billion years ago. In exchange for food and shelter, the bacteria helped cells break nutrients into energy. These helpful tenants became modern mitochondria: the power-plants inside all cells of nearly every animal, plant, fungus, and protozoan.

Yet domestic disputes over cellular housekeeping may spur divorce, according to findings from Clark’s lab showing mitochondria moving out.

Graduate student Yelena Bisharyan discovered this while studying an unrelated phenomenon: escape stunts of the fish parasite Ichthyophthirius multifiliis. Clark’s lab had observed these parasitic protozoa avoiding destruction by shaking off attacking antibodies and exiting their hosts and wanted to see how they escaped.

“Attacking antibodies bind to the parasite’s cell surface,” said Clark. “We suspected that when antibodies attach, the parasite can shed them by breaking off its surface proteins – sort of like a lizard shedding its tail.”

tetrehymena 2

Tetrahymena, a protozoan, sheds proteins and mitochondria in response to attacking antibodies

Applying antibodies to parasites in culture, Bisharyan observed the reactions of Ichtyophthirius and Tetrahymena, another ciliated protozoan used as a model system to study fundamental biological principles across species.

Using negative staining and electron microscopy techniques, Bisharyan recorded parasites sacrificing their surface proteins to rid themselves of attached antibodies. Yet her images also captured something completely unexpected: intact and fragmented mitochondria coming out of the parasite’s cells.

This surprising finding won Bisharyan an invitation to present at one of the 2011 Gordon Research Conferences, a prestigious international forum showcasing major discoveries across scientific fields.

“Mitochondria experts were very excited to see this,” said Clark. “Over the past 15 years several papers have reported mitochondrial DNA and proteins floating outside mammalian cells. No one knew how or why they got there. What we’ve found in protozoa may help explain similar processes in mammals.”

Mitochondria (m) are pushed to the surface and jettisoned from the cell

mitochondria shed

Mitochondria (red) discovered outside cells

Certain cellular stressors can trigger mitochondrial expulsion, according to Bisharyan’s study. In protozoa, for example, not only antibodies but also heat shock can induce this effect. These stressors elevate calcium levels within the cell, possibly damaging mitochondria and causing them to produce toxic free-radicals.

“Our hypothesis is that mitochondria become poisoned and these protozoa have found a way to rid themselves of the damaged powerplants before they can cause further harm,” said Clark. “We think their behaviour reveals an early adaption to cellular stress that other species may share.”

Mammals and fish parasites may bear little family resemblance these days, but a common ancestor may have equipped both with emergency mitochondria-removal systems. Understanding this process could illuminate new approaches to reducing mitochondria-induced damage in humans and other animals.

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Cornell University College of Veterinary Medicine news

http://vet.cornell.edu/news/Mitochondria.cfm

How ‘promiscuous parasites’ hijack host immune cells

Sept. 19, 2011

By Carly Hodes

Toxoplasma gondii parasites can invade your bloodstream, break into your brain and prompt behavioral changes from recklessness to neuroticism. These highly contagious protozoa infect more than half the world’s population, and most people’s immune systems never purge the intruders.

Toxoplasma gondii

Toxoplasma gondii parasites, green, multiply inside an immune cell that lives in the brain.

Cornell researchers recently discovered how T. gondii evades our defenses by hacking immune cells, making it the first known parasite to control its host’s immune system. Immunologists from the College of Veterinary Medicine published the study Sept. 8 in PLoS-Pathogens, describing a forced partnership between parasite and host that challenges common conceptions of how pathogens interact with the body.

Eric Denkers

Dr. Eric Denkers

“Toxoplasma is an especially promiscuous parasite,” said Eric Denkers, professor of immunology. “It infects nearly all warm-blooded species, most nucleated cell types and much of the human population. Although it lives in vital brain and muscle tissues, it usually causes no obvious reaction. Infection can seriously harm people with weak immune systems, yet most hosts experience no overt symptoms because Toxoplasma has found a way to coerce cooperation.”

Famous for its manipulative powers, T. gondii has been shown to alter the brain chemistry of rodents so that they fearlessly pursue cats. Cats eat the rodents, delivering the parasites to their breeding ground in feline intestines. Similar manipulations have surfaced in human studies linking T. gondii infections to behavioral and personality shifts, schizophrenia and population variations, including cultural differences and skewed sex ratios. Denkers’ study maps T. gondii’s newfound ability to manipulate cells in the immune system at the molecular level.

Toxoplasma parasites

Toxoplasma parasites forming a walled cyst in a mouse brain, where they release chemicals that can affect behavior.

“We found that Toxoplasma quiets its host’s alarm system by blocking immune cells from producing certain cytokines, proteins that stimulate inflammation,” said Denkers. “Cytokines are double-edged swords: They summon the immune system’s reinforcements, but if too many accumulate they can damage the body they’re trying to defend. An unregulated immune response can kill you.”

When immune cells meet intruders, they release cytokines that summon more immune cells, which produce more cytokines, rapidly causing inflammation. T. gondii must allow cytokines to trigger enough of an immune response to keep its own numbers in check and ensure host survival. But too many cytokines cause an overwhelming immune response that could damage the host or eliminate the parasites.

cytokine production in uninfected immune cells

Green stain highlights cytokine production in uninfected immune cells. Cells infected with Toxoplasma parasites, orange, cannot make cytokines.

“Toxoplasma hijacks immune cells to enforce a mutually beneficial balance,” Denkers said. “Until recently we thought it walled itself away inside cells without interacting with its environment. It’s now clear that the parasite actively releases messages into cells that change cell behavior.”

To prove this, Barbara Butcher, a senior research associate working with Denkers, exposed immune cells in the lab to bacterial factors that typically stimulate the release of inflammatory cytokines.

“Cells infected with Toxoplasma produced no messages to trigger inflammation,” Denkers said. “Our colleagues at Stanford University found that Toxoplasma produces a specific protein called ROP16 to suppress inflammatory responses. Collaborating with parasitologists at Dartmouth Medical School, we found that Toxoplasma sends ROP16 to infiltrate communication channels in immune cells, causing them to lower cytokine production.

“We are excited to have found the first non-bacterial pathogen able to exert this kind of control,” said Denkers. “If Toxoplasma can do this, maybe other parasites can too. This is the first case where the whole process of immune system manipulation is close to being completely mapped out at the molecular level.”

That map may help steer future investigations into how pathogens interact with hosts, unveiling the inner workings of a spectrum of infectious diseases.

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/toxoplasma.cfm

Media Hits:

Cornell Chronicle

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

Answerclopedia

http://answerclopedia.com/promiscuous-parasites-hijack-host-immune-cells.html

Medical Xpress

http://medicalxpress.com/news/2011-09-promiscuous-parasites-hijack-host-immune.html

MyScience

http://www.myscience.cc/news/promiscuous_parasites_hijack_host_immune_cells-2011-cornell

Times of India

http://timesofindia.indiatimes.com/life-style/health-fitness/health/Promiscuous-parasites-make-you-reckless/articleshow/10079594.cms

NewKerala

http://www.newkerala.com/news/2011/worldnews-72626.html

LabSpaces

http://www.labspaces.net/113581/Researchers_discover_how__promiscuous_parasites__hijack_host_immune_cells

TopNews.in

http://www.topnews.in/health/promiscuous-parasites-can-make-you-reckless-213177

http://www.citybengaluru.com/promiscuous-parasites-can-make-you-reckless/

http://www.indiatalkies.com/2011/09/promiscuous-parasites-reckless.html

Amwayagent

http://www.amwayagent.com/researchers-discover-how-promiscuous-parasites-hijack-host-immune-cells.html

InfectionControlToday

http://www.infectioncontroltoday.com/news/2011/09/researchers-discover-how-promiscuous-parasites-hijack-host-immune-cells.aspx

ScienceDaily

http://www.sciencedaily.com/releases/2011/09/110921120056.htm

NewsWise

http://www.newswise.com/articles/researchers-discover-how-promiscuous-parasites-hijack-host-immune-cells

Science Codex

http://www.sciencecodex.com/researchers_discover_how_promiscuous_parasites_hijack_host_immune_cells

MedicalNewsToday

http://www.medicalnewstoday.com/releases/234798.php

NewsBlaze

http://newsblaze.com/story/2011092108200300003.wi/topstory.html

RedOrbit

http://www.redorbit.com/news/science/1112386702/researchers-discover-how-promiscuous-parasites-hijack-host-immune-cells

New York Ag

http://www.newyorkagconnection.com/story-state.php?Id=835&yr=2011

Biocompare

http://news.biocompare.com/News/NewsStory/394349/Researchers-Discover-How-promiscuous-Parasites-Hijack-Host-Immune-Cells.html

Science Newsline

http://www.sciencenewsline.com/biology/2011092117140007.html

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http://www.sify.com/news/promiscuous-parasites-can-make-you-reckless-news-international-ljwpuqjjiei.html

News Medical

http://www.news-medical.net/news/20110922/Cornell-researchers-identify-how-T-gondii-controls-hosts-immune-system.aspx

http://happinessbeyondthought.blogspot.com/2011/09/brain-parasite-in-most-of-us-prompts.html

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/