Discovery of Hepatitis C Virus in Canines Opens New Doors for Research on Deadly Human Pathogen

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Recent research from the Center for Infection and Immunity (CII) at Columbia University’s Mailman School of Public Health, the University of Edinburgh, and the Center for the Study of Hepatitis C and Pfizer Veterinary Medicine reports the discovery of a hepatitis C-like virus in dogs. The identification and characterization of this virus gives scientists new insights on how hepatitis C in humans may have evolved and possible a model system to study how it causes disease.

Human hepatitis C virus (HCV) affects approximately 200 million people worldwide. According to the Centers for Disease Control and Prevention (CDC), 3.2 million people in the United States are chronically infected. The majority of these patients do not even know that they are carrying the virus. This serves as a source of infection for others. (Sciencedaily.com) HCV causes liver disease, fibrosis, cirrhosis, and liver cancer. HCV is most often transmitted following large or repeated exposure to infected blood. Persons who use injections drugs, are HIV-positive, or are children of infected mothers have the highest risk of infection.

Researchers at Pfizer were investigating virus outbreaks in dogs in shelters across the United States. They swabbed the noses of dogs sick with respiratory diseases and searched for viruses. In some cases they could not isolate a known virus, so they sent samples to the Center for Infection and immunity at Columbia University, where researchers specialize in finding new viruses. The Columbia center found that six of nine dogs in one outbreak and three of five in another shared the same unknown virus. Nasal swabs from 60 healthy dogs showed no sign of it. Amit Kapoor, a Columbia virologist, compared the genetic material of the new virus to known ones. His analysis revealed it was closely related to the hepatitis C virus (HCV for short). “I was not expecting anything like HCV. Before researchers thought that it had evolved from a primate virus, because chimpanzees can be experimentally infected with hepatitis C. But as Dr. Kapoor and Peter Simmonds of the University of Edinburgh analyzed more genetic data, the link continued to hold. Dr. Kapoor and his colleagues have called the new virus canine hepacivirus, or CHV for short.

Using a sequencing platform provided by Roche 454 Life Sciences and state-of-the-art molecular techniques, Dr. Kapoor determined that like HCV, CHV’s genome contained RNA secondary structures called GORS that allow viruses to chronically infect their natural hosts. The sequence of genes that encode proteins involved in virus infection and replication were very similar between HCV and CHV. (Sciencedaily.com)The Columbia researchers collaborated with hepatitis C experts at Rockefeller University in New York to compare the two viruses. Canine hepacivirus infects the airways of dogs and is present at low levels in the liver.

The discovery of canine hepatitis C (CHV) is the first known instance of hepatitis-like infection in non-human primates and suggests that the virus may have been introduced into human populations through contact with dogs or some other related species more than 500 years ago.

Viral zoonoses, infections that are transmitted from animals to humans, account for about 70% of fuman emerging infectious diseases. Although transmission between species is uncommon, sustained contact over time can increase the likelihood that a virus adapted to infect humans will evolve. Whether humans and dogs were independently infected with an ancestral virus by another species, or whether dogs infected humans, or vice verse, cannot be determined from this study.

Until recently, studies into how hepatitis C causes disease in humans have been limited by lack of animal and cell culture models. The identification and characterization of CHV allows the beginning of a new animal model for hepatitis C. This provides new tools for understanding how this virus causes disease and will facilitate drug and vaccine research and development.

Sources:

http://www.sciencedaily.com/releases/2011/05/110523152344.htm

http://www.nytimes.com/2011/05/31/health/31hepatitis.html?_r=2&scp=1&sq=carl%20zimmer&st=cse

98.6 Degrees Fahrenheit Ideal Temperature for Keeping Fungi Away and Food at Bay

The core or normal body temperature for a human being is 98.6 degrees Fahrenheit or 37 degrees Celsius. Body temperature based on an individual may vary but each person's core temperature remains fairly consistent. Metabolism rate fluctuates a human's body temperature. The slower the metabolic rate the lower the normal body temperature and the faster the metabolic rate the higher the normal body temperature. Our body temperatures are always lowest in the morning because of the long period of rest and of course the highest late at night from the day's activities and caloric intake.

Two researchers at Albert Einstein College of Medicine of Yeshiva University found that our 98.6° F (37° C) body temperature strikes a near perfect balance: warm enough to ward off fungal infection but not so hot that we need to eat nonstop throughout the day to maintain our metabolism. "One of the mysteries about humans and other advanced mammals has been why they are so hot compared with other animals," said study co-author Arturo Casadevall, M.D., Ph.D., professor and chair of microbiology & immunology at Einstein. "This study helps to explain why mammalian temperatures are all around 37° C." Dr. Casadevall also holds the Leo and Julia Forchheimer Chair in Microbiology and Immunology. Thousands of fungal species infect reptiles, amphibians and other cold-blooded animals. Mammals like ourselves are only infected by a few hundred from this fungal species. The warmer the core temperature, the harder it is for fungal species to thrive and therefore infect an animal or human. Dating back millions of years ago, this could be one of the reasons why mammals survived and dinosaurs didn't.

In this study, Dr. Casadevall and his Einstein coauthor, Aviv Bergman, Ph.D., professor and founding chair of systems & computational biology, devised a mathematical model that analyzed the benefits gained by body temperatures that protect against fungi versus the costs (in terms of extra food consumption) required to maintain body temperatures between 30° and 40° C. The optimal temperature for maximizing benefits while minimizing costs was found to be 36.7° C, which closely approximates normal body temperature (98.06° F).

Being able to protect yourself or at least be less susceptible to fungal infections carries with it a lot of benefits. Some fungi can cause serious diseases in humans, several of which may be fatal if untreated. These include aspergilloses, candidoses, coccidioidomycosis, histoplasmosis and mycetomas. Other fungi can attack your eyes, nails, hair. Some fungi infections that you may be sound familiar are ringworm and athlete's foot which are skin infections.

"This study is a good example of how mammalian evolution has been driven by both external biological factors and internal physiological constraints," said Dr. Bergman.

References

A. Bergman, A. Casadevall. Mammalian Endothermy Optimally Restricts Fungi and Metabolic Costs. mBio, 2010; 1 (5): e00212-10 DOI: 10.1128/mBio.00212-10

http://www.sciencedaily.com/releases/2010/12/101222121610.htm

http://www.einstein.yu.edu/home/default.asp

Cook GC; Zumla AI (2008). Manson's Tropical Diseases: Expert Consult. Saunders Ltd. p. 347.

Drug Resistant Tuberculosis

Tuberculosis has been a problem for mankind for at least 7000 years. From Neolithic man and Egyptian times, Tuberculosis has caused people to slowly waste away. Before antibiotics were invented, people were sent away to sanotoriums. These were places isolated from the general population where infected patients would get plenty of fresh air and good nutrition, thought to be the best treatment at the time. With the advent of antibiotics, man found a new lease on his struggle with tuberculosis. He is now finding out how tenuous his hold on that lease is. Newly evolved strains of TB are proving resistant to once common therapy and are causing new treatments to be sought.

Tuberculosis is a gram positive bacteria that is spread among humans through the air. It is especially a problem in enclosed spaces , such as jails, homeless shelters, dormitories, etc. Once contracted, tuberculosis may lie dormant for quite some time, which is called latent TB. Latent TB is non-transmittable, and can persist as such for many years. During this time it may be treated with oral antibiotics for a duration of four to nine months. Once the tuberculosis infection becomes active it is spread by airborne transmission of the bacteria in droplets of phlegm, mucous, and saliva. At this point the infection is fairly contagious and is often spread in enclosed environments like cafeterias, jails, homeless shelters, and airplanes. With an active tuberculosis experiences night sweats and fevers, a persistent cough, hemoptysis (coughing up blood), and poor appetite. If the infection is discovered, a person may be treated in a hospital. They are isolated in a negative pressure room where unexposed air is constantly drawn into the room and expelled through a filter sufficient to remove the bacteria. Health care workers must wear a fitted N-95 mask that also filters the bacteria. The tuberculosis infection is then treated with intravenous antibiotics . Three or more antibiotics are used to treat tuberculosis as it develops a resistance to a single antibiotic when it is used alone. Three or more antibiotics create a greater chance that all of the tuberculosis bacteria within the body will be killed in a short period of time before they are able to mutate and develop resistance.

Unfortunately, antibiotic resistance in tuberculosis has developed at a quicker pace than new antibiotics, with some strains becoming increasingly resistant in recent years. Currently there are three types of drug resistant TB. Drug resistant TB is tuberculosis that has developed a resistance to one of the first-line antibiotics used to treat it. Multi-Drug Resistant TB (MDR TB) has developed a resistance to isoniazid and rifampicin, two drugs used to treat all cases of TB. Extensively-Drug resistant TB (XDR TB) has developed a resistance to both isoniazid and rifampicin. Recently there have been advances in diagnosing TB and identifying its multi-drug resistant form. This will hopefully result in quicker treatment ofmulti-drug resistant TB with the appropriate course of antibiotics. This should reduce additional drug resistance and result in better patient outcomes.

Sources:

NIH/National Institute of Allergy and Infectious Diseases (2010, September 2). New TB diagnostic proves effective, expedient, study finds. ScienceDaily. Retrieved June 11, 2011, from http://www.sciencedaily.com­ /releases/2010/09/100901171559.htm

http://www.cdc.gov/tb/topic/drtb/default.htm

Enterohaemorrhagic Escherichia Coli 0104:H4

In Germany, there has been a recent outbreak in the bacteria, E. Coli. This epidemic has many worried because this strain of E. coli has never been seen in an outbreak before and there is no known cure for it so far. This outbreak of disease has killed 30 people to date and has more than 2,800 people sick. Modern history has not experienced such a devastation from an disease epidemic yet.

E. coli is a gram negative, rod-shaped bacterium. Most E. coli bacteria are harmless. They are in the intestines of all warm-blooded mammals. They live in the intestinal flora and are beneficial for the host. They produce potassium and also help prevent harmful bacteria from taking up residence in the intestine. However, there are different types of E. coli. A type of E. coli that isn't harmless, but actually life threatening, is called Enterohaemorrhagic. They produce toxins called Shiga toxins or verotoxins. These toxins damage the kidneys and blood cells. The E. coli bacteria are able to attach to an intestinal wall and slowly release shiga toxins making the host sick. The infection can cause cramps, bloody diarrhea, nausea and vomiting. The 0104:H4 infection hasn't been connected to causing vomiting. For those with a compromised immune system, such as the elderly and children, it can be life threatening. HUS, Haemolytic uraemic syndrome, is a complication caused by an E. coli infection. This syndrome can cause kidney failure and hemolytic anemia. People with HUS often need blood transfusions or dialysis.

The 0104:H4 strain of E. Coli is resistant to most antibiotics. However, antibiotics are usually not used to treat Enterohaemorrhagic E. coli because the antibiotics can be toxic themselves to the kidney and also they can harm the good bacteria in the intestines, making it so that the E. coli can spread farther. In fact, certain antibiotics can double the harm of E. coli. The antibiotic can turn on the bacterial gene that produces shiga toxin and then when it kills the bacteria, it kills bacteria that are full of toxin and making the effect of E. coli worse.

Right now several ideas are being tested to find a way to stop the Enterohaemorrhagic Escherichia Coli 0104:H4 from claiming more lives. There are German doctors in the process of trying the drug Soliris to stop hemolysis in the patients with the E. coli infections.

It is possible to get E. coli by consuming undercooked meats, raw milk, contaminated water and contaminated foods, such as raw vegetables and fruit. The infection can occur through contact with feces that are contaminated. The bacteria don’t die until cooked to the temperature of 70 degrees C (158 degrees F).

There are several ways to protect against getting E. coli. They are: washing hands well before handling food and after using the bathroom, washing fruits and vegetables well, by cooking all raw meats well, and by not drinking raw milk or contaminated water.

Resources

http://www.examiner.com/science-news-in-national/new-killer-e-coli-superbug-germany-treatment-issues#ixzz1OjpyhMum

http://www.webmd.com/a-to-z-guides/e-coli-infection-topic-overview?page=2

http://www.euro.who.int/en/what-we-publish/information-for-the-media/sections/latest-press-releases/germany-investigates-outbreak-of-haemolytic-uraemic-syndrome

http://www.sciencedaily.com/releases/2011/06/110602184851.htm

http://www.ibtimes.com/articles/157201/20110603/e-coli-outbreak-us-scientists-warn-against-hysteria-but-say-anti-biotics-are-not-the-solution.htm

Methicillin Resistant Staphylococcus Aureus (MRSA) (S. aureus)
~Beth Morris

Over the past number of years, many bacteria have become resistant to antibiotics in the U.S. Penicillin, oxacillin and amoxicillin for example have become ineffective against many pathogens. Methicillin Resistant Staphylococcus Aureus (MRSA) is highly known for its resistance to antibiotics. MRSA, staph bacteria are more commonly known as skin infections and are potentially fatal depending on the severity. MRSA also has been known to cause pneumonia, toxic shock syndrome (TSS) and food and blood poisoning (Bolton). Symptoms of MRSA appear on parts of the body such as the neck, groin and underarm areas. They are very painful boil-like pustules and are caused from contact to an infected person or by sharing personal hygiene items. Penicillin, introduced to doctors in the 1940’s served as a temporary fix to the bacteria before resistant strains appeared. As more antibiotics were founded S. aureus found itself resistant to them as well; Methicillin being yet another. There are two types of MRSA, 1 of which is hospital related and the other is community related. Approximately 85% of all MRSA cases occur within a hospital setting. MRSA is not prejudice to its host. It can and will infect anyone from child to the elderly and from those in the health care field to athletes.

In an effort to understand MRSA more deeply a group of scientists collected samples from infected individuals from across the world and sequenced the bacteria’s genome. Their finding indicated that no two individuals developed the same type of infection and that none of the bacteria were identical. This group of scientist found that mutation of the MRSA strain collected a singular letter change in the DNA sequence approximately every 6 weeks.

As MRSA can be spread from objects to open wounds and even through ones nasal passages; it is important to practice adopt good hygiene habits by disinfecting areas, wash your hands frequently and keep any open sores covered with bandages to prevent contracting the bacteria.

(Powell, 2010)

(Mary Pat Bolton)

(CDC)

(The PEW Charitable Trusts Human Health and Industry)

CDC. (n.d.). MRSA Infections. Retrieved 4 30, 2011, from Centers for Disease control and Prevention: http://www.cdc.gov/mrsa/symptoms/index.html

Mary Pat Bolton, M. (n.d.). What is Methicillin-Resistant Staphylococcus aureus. Retrieved 4 30, 2011, from Biology Teacher Resources from Baylor College of Medicine: http://www.bioedonline.org/slides/slide01.cfm?tk=53&dpg=2

Powell, D. (2010, 1 21). Tracking MRSA evolution and transmission. Retrieved 4 30, 2011, from http://www.eurekalert.org/pub_releases/2010-01/wtsi-tme011510.php

The PEW Charitable Trusts Human Health and Industry. (n.d.). Retrieved 4 30, 2011, from The Cause of Antibiotic Resistance: http://www.saveantibiotics.org/ourwork.html#causes

Protein in Monkeys Makes Them Resistant to HIV

Recent research at the University of Geneva and the University of Zurich have discovered that a protein called, TRIM5 is responsible for making certain species of monkeys resistant to HIV. It has been known for a few years that this protein was able to resist HIV in monkeys, but it was unclear how this was possible.

In the past few weeks recent discoveries have been made as to how TRIM5 is capable of resisting HIV. "The protein prevents the HI virus from multiplying once it has entered the cell" (ScienceDaily). This is possible because TRIM5 is able to immediately recognize when HIV enters the body and it triggers an immune response. This response is triggered through the innate immune system which differs from the adaptive immune system because it "is already able to eliminate pathogens as soon as it comes into contact with them" (ScienceDaily).

The research done at these universities has revelead how TRIM5 prevents HIV from multiplying. When HIV enters a cell, it is arranged in a complex arrangement that TRIM5 recognizes and attaches itself to. Once TRIM5 is attached it is able to trigger certain signal molecules called "polybiquitin chains" that start an anti-viral reaction to the HIV inside the cell. After this process occurs, the cell can begin to get rid of cells with HIV by "releasing messenger substances (cytokines)" (ScienceDaily).

Although this study showed that "rhesus" monkeys, also called night monkeys, were able to resist HIV, it provides new possibilities in the prevention and treatment of HIV. TRIM5 is not a protein that is unique to monkeys, humans have this protein as well. Even though it does not appear to be as effective in resisting HIV as it does in these monkeys it brings scientists closer to finding ways to fight HIV.

References:

http://www.sciencedaily.com/releases/2011/04/110420143624.htm

http://biology.kenyon.edu/slonc/gene-web/Lentiviral/Lentiv2.html (image)

Nanoparticles Target Cancer Cells

By: Abby VanFossen

Sandia National Labarotories, the University of New Mexico and the UNM Cancer Research and Treatment Center have developed a method of introducing cancer killing drugs through silica nanoparticles directly to cancerous cells. These Nanoparticles are able to store large amounts and varieties of chemicals within their honeycomb shape.

The particles are described as having a nanoporous core with a high surface area and an encapsulating lipid bi-layer (liposome). The nanoparticles and the surrounding cell-like membranes formed from liposomes together become the combination referred to as a protocell: the membrane seals in the deadly cargo and is modified with molecules (peptides) that bind specifically to receptors overexpressed on the cancer cell's surface. (Too many receptors is one signal the cell is cancererous.) The nanoparticles provide stability to the supported membrane and contain and release the therapeutic cargo within the cell. The lipids also serve as a shield that restricts toxic chemotherapy drugs from leaking from the nanoparticle until the protocell binds to and takes hold within the cancer cell. This means that few poisons leak into the system of the human host, if the protocells find no cancer cells. This cloaking mitigates toxic side effects expected from conventional chemotherapy.

This method is currently being tested on human cells in vivo (occurring or carried out in a living organism) and will shortly be tested in mouse tumors. Estimates are that this method will be 10,000 times more effective than current liposome delivery methods and may be available in as early as 5 years. This will be the first work to show targetted delivery of nanoparticles to cancers supported in part by a grant from the National Cancer Institute's Alliance for Nanotechnology in Cancer .(1)

This method provides hope for easier treatment of some cancers. As well, the specific targetting that is being attempted will reduce the side effects of cancer treating drugs in the patient. This may lead to better long term health for the cancer survivor as well as less painful treatments.

1. Carlee E. Ashley, Eric C. Carnes, Genevieve K. Phillips, David Padilla, Paul N. Durfee, Page A. Brown, Tracey N. Hanna, Juewen Liu, Brandy Phillips, Mark B. Carter, Nick J. Carroll, Xingmao Jiang, Darren R. Dunphy, Cheryl L. Willman, Dimiter N. Petsev, Deborah G. Evans, Atul N. Parikh, Bryce Chackerian, Walker Wharton, David S. Peabody, C. Jeffrey Brinker. The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers. Nature Materials, 2011