What are the symptoms of swine flu (H1N1)?

Symptoms of swine flu are similar to most influenza infections: fever (100F or greater), cough, nasal secretions, fatigue, and headache, with fatigue being reported in most infected individuals. Some patients also get nausea, vomiting, and diarrhea. In Mexico, many of the patients are young adults, which made some investigators speculate that a strong immune response may cause some collateral tissue damage. Some patients develop severe respiratory symptoms and need respiratory support (such as a ventilator to breathe for the patient). Patients can get pneumonia (bacterial secondary infection) if the viral infection persists, and some can develop seizures. Death often occurs from secondary bacterial infection of the lungs; appropriate antibiotics need to be used in these patients. The usual mortality (death) rate for typical influenza A is about 0.1%, while the 1918 “Spanish flu” epidemic had an estimated mortality rate ranging from 2%-20%. Swine flu in Mexico (as of April 2009) has had about 160 deaths and about 2,500 confirmed cases, which would correspond to a mortality rate of about 6%, but these initial data have been revised and the mortality rate currently in Mexico is estimated to be much lower. By June 2009, the virus had reached 74 different countries on every continent except Antarctica, and by September 2009, the virus had been reported in most countries in the world. Fortunately, the mortality rate as of October 2009 has been low but higher than for the conventional flu (average conventional flu mortality rate is about 36,000 per year; projected novel H1N1 flu mortality rate is 90,000 per year in the U.S. as determined by the president’s advisory committee).

Why is swine flu (H1N1) now infecting humans?

Many researchers now consider that two main series of events can lead to swine flu (and also avian or bird flu) becoming a major cause for influenza illness in humans.

First, the influenza viruses (types A, B, C) are enveloped RNA viruses with a segmented genome; this means the viral RNA genetic code is not a single strand of RNA but exists as eight different RNA segments in the influenza viruses. A human (or bird) influenza virus can infect a pig respiratory cell at the same time as a swine influenza virus; some of the replicating RNA strands from the human virus can get mistakenly enclosed inside the enveloped swine influenza virus. For example, one cell could contain eight swine flu and eight human flu RNA segments. The total number of RNA types in one cell would be 16; four swine and four human flu RNA segments could be incorporated into one particle, making a viable eight RNA segmented flu virus from the 16 available segment types. Various combinations of RNA segments can result in a new subtype of virus (known as antigenic shift) that may have the ability to preferentially infect humans but still show characteristics unique to the swine influenza virus (see Figure 1). It is even possible to include RNA strands from birds, swine, and human influenza viruses into one virus if a cell becomes infected with all three types of influenza (for example, two bird flu, three swine flu, and three human flu RNA segments to produce a viable eight-segment new type of flu viral genome). Formation of a new viral type is considered to be antigenic shift; small changes in an individual RNA segment in flu viruses are termed antigenic drift and result in minor changes in the virus. However, these can accumulate over time to produce enough minor changes that cumulatively change the virus’ antigenic makeup over time (usually years).

Second, pigs can play a unique role as an intermediary host to new flu types because pig respiratory cells can be infected directly with bird, human, and other mammalian flu viruses. Consequently, pig respiratory cells are able to be infected with many types of flu and can function as a “mixing pot” for flu RNA segments (see Figure 1). Bird flu viruses, which usually infect the gastrointestinal cells of many bird species, are shed in bird feces. Pigs can pick these viruses up from the environment and seem to be the major way that bird flu virus RNA segments enter the mammalian flu virus population.

Vitamin D helps brain to work well at later age

Vitamin D may have a key role in helping the brain to keep working well in later life, suggests research published ahead of print in the Journal of Neurology Neurosurgery and Psychiatry.

Previous research indicates that inadequate vitamin D intake may be linked to poorer mental agility in the ageing brain, but the results have been inconsistent.
The researchers base their current findings on just over 3000 European men between the ages of 40 and 79, who were all part of the international European Male Ageing Study, drawn from eight different cities across Europe.

Their mental agility was assessed using a range of tests, designed to measure memory and speed of information processing as well as mood and physical activity levels, both of which affect mental agility.

Blood samples were then taken to measure circulating levels of vitamin D, which is obtained through dietary sources and by exposure to sunlight.

High circulating vitamin D levels were associated with high scores on the memory and information processing tests, but after adjusting for mood and physical activity, the association remained for only one of the two information processing tests.

Low vitamin D levels were associated with poor scores, with levels of 35 nmol/litre or under marking the threshold of poorer performance.

Experimental data point to the biological plausibility for an association between low circulating levels of vitamin D and poorer mental agility, but exactly how the two might be connected is not clear, say the authors.

Possible suggestions include vitamin D’s role in increasing certain hormonal activity or the protection of neurones and chemical signalling pathways.

The findings show that the magnitude of the association between vitamin D level and mental agility was comparatively small, say the authors.

But if it were possible to stave off the effects of ageing on the brain with vitamin D supplements, then the implications for population health could be quite significant, they contend, because many people, particularly in older age, arevitamin D deficient.

Acupuncture eases chronic low back pain

Acupuncture can help people with chronic low back pain feel less bothered by their symptoms and function better in their daily activities, according to the largest U.S. randomized trial of its kind, published in the May 11, 2009 Archives of Internal Medicine. But the SPINE (Stimulating Points to Investigate Needling Efficacy) trial raises questions about how the ancient practice actually works.
Compared to the group that got usual care, results were similar for all three of the SPINE trial’s acupuncture groups: individualized, standardized, and simulated (without going through skin). Of the people who got any kind of acupuncture, an extra one in five were functioning significantly better at the end of the seven-week treatment—and an extra one in eight were still functioning better at one year.

“This study suggests that acupuncture is about as effective as other treatments for chronic back pain that have been found helpful,” said SPINE trial leader Daniel C. Cherkin, PhD, a senior investigator at Group Health Center for Health Studies in Seattle. “But we found that simulated acupuncture, without penetrating the skin, produced as much benefit as needle acupuncture—and that raises questions about how acupuncture works.”

The SPINE trial included 638 adult patients at two nonprofit health plans: Group Health Cooperative in Seattle and Northern California Kaiser Permanente in Oakland. They all rated the “bothersomeness” of their chronic low back pain as at least a 3 on a 0-to-10 scale. None of them had received acupuncture before. They were randomly assigned to one of four groups:

* Individualized needle acupuncture, involving a customized prescription for acupuncture points from a diagnostician
* Standardized needle acupuncture, using a single prescription for acupuncture points on the back and backs of the legs, which experts consider generally effective for chronic low back pain
* Simulated acupuncture on those same standardized points, mimicking needle acupuncture but instead of a needle using a toothpick in a needle guide tube without penetrating the skin
* Usual care, which is the standard medical care they would have gotten anyway—and that all patients in all groups received

Everyone in the three acupuncture groups (individualized, standardized, or simulated) was treated twice a week for three weeks, and then weekly for four weeks. At eight weeks, half a year, and one year, researchers measured back-related dysfunction and how much symptoms bothered patients.

The SPINE team found that at eight weeks all three acupuncture groups were functioning substantially better, while the group getting only usual care was functioning only slightly better. Dysfunction scores improved significantly more for all three acupuncture groups than for the usual care group. These benefits lasted for a year, although they waned over time.

Notably, the outcomes for groups that received the needle and simulated forms of acupuncture did not differ significantly. So, although acupuncture effectively treated low back pain, that therapeutic benefit seemed to require neither tailoring acupuncture needle sites to an individual patient nor inserting needles into the skin.

“We don’t know precisely why people got back pain relief from the simulated acupuncture,” said Cherkin’s co-author Karen J. Sherman, PhD, MPH, a senior investigator at Group Health Center for Health Studies. “Historically, some types of acupuncture have used non-penetrating needles. Such treatments may involve physiological effects that make a clinical difference.” Or it might be all about the mind-body connection, she said: “Maybe the context in which people get treatment has effects that are more important than the mechanically induced effects.”

Western medicine does not have highly effective medical treatments for chronic back pain, Cherkin said. Back pain is the number-one reason that Americans use complementary and alternative medicine (CAM), including acupuncture.

The National Center for Complementary and Alternative Medicine (NCCAM), part of the National Institutes of Health, funded the SPINE trial.

“The findings of this research show that acupuncture-like treatments, including simulated acupuncture, can elicit positive responses,” said Josephine P. Briggs, MD, director of NCCAM. “This adds to the growing body of evidence that something meaningful is taking place during acupuncture treatments outside of actual needling. Future research is needed to delve deeper into what is evoking these responses.”

Cherkin and Sherman’s SPINE trial co-authors were Richard A. Deyo, MD, MPH, of Oregon Health & Science University in Portland; Partap S. Khalsa, DC, PhD, of NCCAM’s Division of Extramural Research; Andrew L. Avins, MD, MPH, Luisa Hamilton, MD, and Alice Pressman, MS, of NorthernCalifornia Kaiser Permanente in Oakland; William E. Barlow, PhD of Cancer Research and Biostatistics and Group Health Center for Health Studies; and Laura Ichikawa, MS, Janet H. Erro, RN, MN, Kristin Delaney, MPH, and Rene Hawkes of Group Health Center for Health Studies.

€1 million EU funding for Chinese medicine research

King’s College London – King’s College London successfully led a consortium bid for €995,100 of EU funding for a ground-breaking research project that will play an important role in the unification of Western and Chinese approaches to medicine.

The project entitled ‘Good Practice in Traditional Chinese Medicine Research in the Post-genomic Era’ (GP-TCM) will review the current status of Traditional Chinese Medicine (TCM) research, identify problems and propose solutions by applying modern methods of investigation, as well as providing a forum for the exchange of opinions, experience and expertise among scientists in the EU and China.

The three-year project aims to propose guidelines and priority areas for future research, and will lead to the formation of a new academic society, the European Society of TCM Research, which is to facilitate and foster sustainable EU-China collaboration in this area.

The research consortium consists of 29 beneficiary partner institutions and small-and-medium-sized enterprises from the EU and China. Partnerships with more than 20 additional non-beneficiary institutions, companies and independent experts are further strengthening its research.

Holistic approach

Dr Qihe Xu, Lecturer in the Department of Renal Medicine, Division of Gene and Cell Based Therapy, and coordinator of the project, explains: ‘In contrast to the reductionist approach of Western medicine that is based on modern anatomy and cell and molecular biology, TCM uses a unique theory system and an individualised holistic approach to describe health and disease, which is based on the philosophy of Yin-Yang balance. These two medicine systems disagree with each other in many situations since they observe health from their own limited perspective. GP-TCM aims to inform best practice and harmonise research of the safety and efficacy of TCM, especially Chinese herbal medicines and acupuncture, in the EU.’

‘The project will be divided into ten parts, which will review aspects of quality control, extraction and analysis of Chinese herbal medicines. Discussion fora that explore the role of functional genomics methodology in researching the safety, efficacy and mechanisms of action of Chinese herbal medicines and acupuncture are at the core of this project. New guidelines about good practice and agreed protocols in related research areas will harmonise future TCM research in the EU, and online tools and research resources will be made available to all EU member states. As an open-start and open-ending consortium, we will invite more organisations to become involved in the work.’

Professor Peter Hylands, Head of the Department of Pharmacy and Director of the Centre for Natural Medicines Research, continues: ‘We are delighted to be part of this unique group. In the Centre for Natural Medicines Research at King’s we are examining the application of emerging technologies to the solution of difficult problems in the use of traditional medicines. This forum provides an unparalleled opportunity to share our experiences with Chinese and European colleagues and together to develop a 21st-century road map for the global development of traditional medicines.’

Professor Bruce Hendry, Professor of Renal Medicine, concludes: ‘This programme grant is an excellent opportunity for King’s College London to play a leading role in the unification of Western and Chinese approaches to medicinal therapeutics.’

TCM formula slows kidney failure

CM NEWS – A traditional herbal formula has been proved in lab that it may slow the progression of chronic kidney failure.

The formular tested is called keishibukuryogan in Japanese traditional medicine or Gui Zhi Fu Ling Wan (桂枝茯苓丸) in TCM.

In TCM, Gui Zhi Fu Ling Wan has the functions of “activating blood flow” and “removing blood stasis”. It is commonly used by women with irregular menstruation or menstrual cramps.

Gui Zhi Fu Ling Wan was also proved effective to exert anti-inflammatory effects in ischemia-reperfusion injured rats.

The formula of Gui Zhi Fu Ling Wan is as follows:

* Fu Ling (茯苓, Poria Cocos) 6g
* Gui Zhi (桂枝, Cinnamomum Ramulus) 6g
* Mu Dan Pi (牡丹皮, Paeonia Cortex) 6g
* Tao Ren (桃仁, Persica Semen) 6g
* Chi Shao (赤芍, Paeonia Rubra Radix) 6g

What is Fu Ling? Poria Cocos is a fungus in the Polyporaceae family. It is a wood-decay fungus but has a terrestrial growth habit. It is notable in the development of a large, long-lasting underground sclerotium that resembles a small coconut. This sclerotium (called “Tuckahoe”, or Indian Bread) was used by native Americans as a source of food in times of scarcity.

Fu Ling is collected between July and September. The poria with reddish inner side of the superficial layer is called red poria and the poria with white inner side of the superficial layer is called white poria. The poria produced in Yunnan Province is famous and therefore the drug is also called Yunnan poria Yunling). After collection, it is dried in shade, sliced, and used unprepared.

Property: Sweet and tasteless in flavour, neutral in property, acting on the heart, spleen and kidney channels.

Effects: Inducing diuresis, excreting dampness, invigorating the spleen, replenishing the middle-jiao, and tranquilizing the mind.

A group of Japanese researchers examined the effects of keishibukuryogan on the early stage of progressive renal failure in rats subjected to 5/6 nephrectomy.

Keishibukuryogan was given orally at a dose of 1% (w/w) and 3% (w/w) in chow. Administration of keishibukuryogan was started at 1 week after 5/6 nephrectomy and was continued for 4 weeks.

At the end of the experiment, Azan staining did not reveal any severe histological changes in the kidneys of the nephrectomized rats. On the other hand, significant increases in mRNA expressions of transforming growth factor-β1 and fibronectin related to tissue fibrosis were observed in nephrectomized rats, and they were significantly suppressed by 3% keishibukuryogan treatment.

Against gene expressions related to macrophage infiltration, 3% keishibukuryogan treatment significantly suppressed osteopontin mRNA levels, and monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 mRNA levels showed a tendency to decrease, but without statistical significance.

It was also observed that 3% keishibukuryogan attenuated serum urea nitrogen and urinary protein excretion levels. From these results, it was suggested that keishibukuryogan exerts beneficial effects that result in slowing the progression of chronic renal failure.

Pandemic is a blink away

U of Maryland – A new study by University of Maryland researchers suggests that the potential for an avian influenza virus to cause a human flu pandemic is greater than previously thought. Results also illustrate how the current swine flu outbreak likely came about.

This graphic shows why the Type A virus can’t be eradicated. (U of Maryland)
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As of now, avian flu viruses can infect humans who have contact with birds, but these viruses tend not to transmit easily between humans. However, in research recently published in the Proceedings of the National Academy of Sciences, Associate Professor Daniel Perez from the University of Maryland showed that after reassortment with a human influenza virus, a process that usually takes place in intermediary species like pigs, an avian flu virus requires relatively few mutations to spread rapidly between mammals by respiratory droplets.

“This is similar to the method by which the current swine influenza strain likely formed,” said Perez, program director of the University of Maryland-based Prevention and Control of Avian Influenza Coordinated Agricultural Project, AICAP. “The virus formed when avian, swine, and human-like viruses combined in a pig to make a new virus. After mutating to be able to spread by respiratory droplets and infect humans, it is now spreading between humans by sneezing and coughing.”

This is the influenza A virus. (U of Maryland)

In his study, Perez used the avian H9N2 influenza virus, one that is on the list of candidates for human pandemic potential. Using reverse genetics, a technique whereby individual genes from viruses are separated, selected, and put back together,Perez and his team created a hybrid human-avian virus. Their research hybrid has internal human flu genes and surface avian flu genes from the H9N2 virus. Though it comes from a different strain of avian flu than the one that contributed to the hybrid virus now causing the swine flu outbreak, Perez’s research virus is similar in origin to the swine flu virus, in that both involved a combination of avian and human influenza viruses.

Perez infected ferrets (considered a good model for human influenza transmission) with the virus he created, and allowed the virus to mutate in the species. Before long, healthy ferrets that shared air space but not physical space with the infected ferret had the virus, showing that the virus had mutated to spread by respiratory droplets.

When the genetic sequences of the mutant virus and original hybrid virus were compared, the only differences were five amino acid mutations, three on the surface, and two internally. Two of the surface mutations were determined to be solely responsible for supporting respiratory droplet transmission. Because so few mutations were necessary to make the hybrid H9N2 transmissible this way, they concluded that after an animal-human hybridinfluenza virus forms in nature, a human pandemic of this virus is potentially just a few mutations away.

“We do not know if the mutations we saw in the lab are the same that have made the H1N1 swine flu transmissible by respiratory droplets,”Perez said. “We will be doing more research on the current swine flu strain to study its specific genetic mutations.”

Perez found that one of the two of the genetic mutations in his lab strain that enabled respiratory transmission between mammals was on the tip of the HA surface protein, one of the sites where human antibodies created in response to current vaccines would bind.

“Because the binding site of the mutant virus is different from the virus upon which the vaccine is modelled, it may mean that current vaccine stocks would not be as effective against the H9N2 mutant strain as previously anticipated,” saidPerez. “We should keep this in mind when designing vaccines for an avian flu pandemic in humans.”

However, scientists cannot predict what the actual mutations will look like if and when they occur in nature, or even which strain ofavian influenza will mutate to infect mammals.

“This is just the tip of the iceberg,” said Perez. “Many more studies have to be done to see which combinations of mutations cause this type of transmission before we can design the appropriate vaccines.”

Perez will be talking this week with the NIH and the CDC to discuss his team’s role in researching the current swine flu virus strain.Perez will likely do studies related to vaccine development, virus transmission between humans and animals, and the pathogenesis of the virus.

A virus vaccine is derived from the virus itself. The vaccine consists of virus components or killed viruses that mimic the presence of the virus without causing disease. These prime the body’s immune system to recognize and fight against the virus. The immune system produces antibodies against the vaccine that remain in the system until they are needed. If that virus, or in some cases a closely similar one is later introduced into the system, those antibodies attach to viral particles and remove them before they have time to replicate, preventing or lessening symptoms of the virus.

The immune system also retains antibodies to a virus after being infected with it, so humans have general immunity to human strains ofavian influenza strains. But humans do not generally have immunity to avian flu strains because they have not been infected by them before. The surface proteins are sufficiently different to escape the human immune response.Avian flu strains are therefore more dangerous for humans because the human immune system cannot recognize the virus or protect against it.

New hope for obesity: TCM cuts fat, long term

A
Chinese medicine seems to be effective in cutting food intake of obese rats and reducing body weight by as much as 33%. The study also suggests that the might provide long term control of body weight.

The study was done at the Center for Advanced Nutrition of Utah State University. According to the researchers, traditional Chinese herbal products were reported to be effective for the treatment of obesity. Among them, Chinese herbal extract Number Ten (NT) is a dietary herbal formulation prepared from rhubarb, ginger, astragalus, red sage and tumeric. This study tested the effectiveness of NT in reducing body weight gain in rats.

What is Number Ten (NT)? Number Ten (NT, which is not a trade name) is a herbal that was reported in a published patent specification to be effective in preventing obesity in rats when it was orally gavage fed.

The effect of NT to reduce body weight was reported in otherwise normal rats that had been made very obese by feeding a high energy diet and also in obese rats that had been treated with monosodium glutamate (to induce hypothalamic lesions). In the former study, an improvement in blood lipid and blood glucose levels was also noted and in the latter one the obesity reducing effect was shown in rats of both genders. In a third study, NT was shown to be effective in attenuating the development of obesity without affecting the gain in lean body tissue in a young growing male rat that had been fed on high fat diet to induce obesity.

The herbal NT is derived from the following formula:

(1) Dahuang (大黃, Rheum officinale Baill.) - 40%
To treat: lack of bowel movement, dysentry, blood clots, tumour, red and painful eyes, abdominal-distention and/or pain, blood in stool, # hemorrhoidal bleeding, urination burning, nose bleeding, coughing out blood, sore extremities, edema, jaundice, lesions, burns and scalding (external application).

(2) Shayuanjili (沙苑蒺藜, 沙苑,
Astragalus complanatus R. Br.) – 13.3%

To treat: spermatorrhea, premature ejaculation, achy loin, dizziness, frequent urination, enuresis vagina discharge, and neurasthenia.

(3) Danshen (丹参, Salvia miltiorrhiza Bge.) – 13.3%
To treat: stroke, angina and heart attack, as an antihypertensive and a sedative.

(4) Shengjiang (生薑, fresh ginger, Zingiber officinale Rosc.) – 6-7%
Functions: Anti-bacteria (especially Salmonella) and anti-trichomoniasis; lowers blood lipids; reduces pain; anti-inflammation; anti- coagulation of platelets; anti-allergic; anti-tumours; and prevents sea sickness etc.

(5) Jianghuang (薑黃, Curcuma longa L.) – 26-27%
Functions: lowers blood lipids; anti-coagulation of platelets; protects liver from toxin; promotes secretion of bile; promotes flow of menses and relieves pain; anti-tumour; anti-inflammatory; anti-oxidation; promotes metabolism of alcohol; antibiotic; antivirus; and protects heart muscle from lack of oxygen etc.
(For more information about curcumins in yellow curry, please read this article.)

The herbs were allowed to soak for 8 hours. The water in the pot with the four-herb mixture was boiled until the volume was reduced by half. A cold rhubarb was then added to the four-herb mixture and heated to just below boiling point for 20 minutes before cooling. After filtering the large particulates from the , the remaining liquid was freeze-dried to a powder form, producing 0.5 g of solids from 10 ml of liquid.

In the present study, 60 female Wistar rats were fed a
high fat diet and acclimated to gavage feeding. The rats were divided into five treatment groups:

1. Control
2. Group 2: NT 1.5 g/day
3. Group 3: NT 0.75 g/day
4. Group 4: pair fed to Group 2
5. Group 5: d-fenfluramine (an appetite suppressant) 2mg/kg

10 rats per group were sacrificed on day 56. Weight,
food intake,
clinical chemistry and body composition were evaluated. 5 animals in the control and 1.5 g/day NT groups were left untreated during a two week recovery period.

The results showed that all treatment groups gained less weight than the control group. These are the reduction percentages:

• Group 3 (NT 0.75g/day) => 24.6%
• Group 2 (NT 1.5g/day) => 33.3%
• Group 5 (d-fenfluramine) =>12.3%
• Group 4 (pair fed) => 33.3%

Moreover, leptin, a protein hormone with important effects in regulating body weight, metabolism and reproductive function, decreased 27.5% to 46.2% in the treatment groups vs. control.

Parametrial fat decreased 14.1% to 55.5% in the NT and pair fed groups vs. control.

The NT groups had soft stools, loss of hair around the mouth and colouration to the urine and stool without evidence of blood or bilirubin (attributed to chromogens in NT). There were no differences between groups in the clinical chemistry.

Reduction in weight gain with NT treatment appears to be caused by reduction in
food intake rather than any metabolic effects, the researchers write.

What’s more encouraging is that the rats treated with high dose NT that were allowed a two week post treatment recovery period did not exhibit any catch-up growth during this period. This finding may suggest a continued response to NT or storage of the active components within the body. It also suggests that the NT treatment may lead to a long lasting reduction in body weight.

The mechanism through which NT reduced
food intake is unknown. There were no clinical symptoms that would cause concern in using this product in humans.

With these strong results, the researchers concluded that this study demonstrate that NT was effective in reducing body weight gain in rats that had been fed a
high fat diet to induce obesity. Its effects are maintained throughout the treatment period as shown in the present study. No toxicity of NT was found in rats although gastric toxicity was reported in humans.

Pandemic is a blink away

U of Maryland – A new study by University of Maryland researchers suggests that the potential for an avian influenza virus to cause a human flu

pandemic is greater than previously thought. Results also illustrate how the current swine flu outbreak likely came about.

As of now, avian flu viruses can infect humans who have contact with birds, but these viruses tend not to transmit easily between humans. However, in research recently published in the Proceedings of the National Academy of Sciences, Associate Professor Daniel Perez from the

University of Maryland showed that after reassortment with a human influenza virus, a process that usually takes place in intermediary species like pigs, an

avian flu virus requires relatively few mutations to spread rapidly between mammals by respiratory droplets.

“This is similar to the method by which the current swine influenza strain likely formed,” said Perez, program director of the University of Maryland-based Prevention and Control of Avian Influenza Coordinated Agricultural Project, AICAP. “The virus formed when avian, swine, and human-like viruses combined in a pig to make a new virus. After mutating to be able to spread by respiratory droplets and infect humans, it is now spreading between humans by sneezing and coughing.”

In his study, Perez used the avian H9N2 influenza virus, one that is on the list of candidates for human

pandemic potential. Using reverse genetics, a technique whereby individual genes from viruses are separated, selected, and put back together, Perez and his team created a hybrid human-avian virus. Their research hybrid has internal human flu genes and surface

avian flu genes from the H9N2 virus. Though it comes from a different strain of

avian flu than the one that contributed to the hybrid virus now causing the swine flu outbreak, Perez’s research virus is similar in origin to the swine flu virus, in that both involved a combination of avian and human influenza viruses.

Perez infected ferrets (considered a good model for human influenza transmission) with the virus he created, and allowed the virus to mutate in the species. Before long, healthy ferrets that shared air space but not physical space with the infected ferret had the virus, showing that the virus had mutated to spread by respiratory droplets.

When the genetic sequences of the mutant virus and original hybrid virus were compared, the only differences were five amino acid mutations, three on the surface, and two internally. Two of the surface mutations were determined to be solely responsible for supporting respiratory droplet transmission. Because so few mutations were necessary to make the hybrid H9N2 transmissible this way, they concluded that after an animal-human hybrid influenza virus forms in nature, a human

pandemic of this virus is potentially just a few mutations away.

“We do not know if the mutations we saw in the lab are the same that have made the H1N1 swine flu transmissible by respiratory droplets,” Perez said. “We will be doing more research on the current swine flu strain to study its specific genetic mutations.”

Perez found that one of the two of the genetic mutations in his lab strain that enabled respiratory transmission between mammals was on the tip of the HA surface protein, one of the sites where human antibodies created in response to current vaccines would bind.

“Because the binding site of the mutant virus is different from the virus upon which the vaccine is modelled, it may mean that current vaccine stocks would not be as effective against the H9N2 mutant strain as previously anticipated,” said Perez. “We should keep this in mind when designing vaccines for an

avian flu

pandemic in humans.”

However, scientists cannot predict what the actual mutations will look like if and when they occur in nature, or even which strain of avian influenza will mutate to infect mammals.

“This is just the tip of the iceberg,” said Perez. “Many more studies have to be done to see which combinations of mutations cause this type of transmission before we can design the appropriate vaccines.”

Perez will be talking this week with the NIH and the CDC to discuss his team’s role in researching the current swine flu virus strain. Perez will likely do studies related to vaccine development, virus transmission between humans and animals, and the pathogenesis of the virus.

A virus vaccine is derived from the virus itself. The vaccine consists of virus components or killed viruses that mimic the presence of the virus without causing disease. These prime the body’s immune system to recognize and fight against the virus. The immune system produces antibodies against the vaccine that remain in the system until they are needed. If that virus, or in some cases a closely similar one is later introduced into the system, those antibodies attach to viral particles and remove them before they have time to replicate, preventing or lessening symptoms of the virus.

The immune system also retains antibodies to a virus after being infected with it, so humans have general immunity to human strains of avian influenza strains. But humans do not generally have immunity to

avian flu strains because they have not been infected by them before. The surface proteins are sufficiently different to escape the human immune response.

Avian flu strains are therefore more dangerous for humans because the human immune system cannot recognize the virus or protect against it.

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