The latest progress in the study of mad cow disease

Article Source: Animal Husbandry and Veterinary Update Time: March 23, 2004 Click Times:

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Chen Ruming, Chen

(Institute of Military Medicine, jinan military area command International Logistics Department, Jinan 2500 14)

Abstract: Since the discovery of mad cow disease, it has spread from Britain to the whole of Europe, and recently to several Asian countries. Scientists have found that it may be transmitted to humans, causing people to be infected with a new type of Creutzfeldt-Jakob disease. At present, the research on mad cow disease has made a breakthrough. In this paper, the epidemiology and etiology of mad cow disease, the correlation between mad cow disease and Creutzfeldt-Jakob disease and the problems to be discussed were reviewed.

Keywords: mad cow disease; Epidemiology; Virus-free; Creutzfeldt-Jakob disease

China library classification number: S858.23 document identification number: Part A number: 0529-5130 (2004) 02-004l-04.

Mad cow disease is the common name of bovine spongiform encephalopathy (BSE). The first case of mad cow disease 1986 1 1 was found in Britain in June. In a few short years, it spread from Britain to France, Germany and other western European countries, and then to Europe in the 1990s. Recently, it has spread to Asia. Japan and South Korea have successively diagnosed 4 cases of mad cow disease and several cases of "mad cow disease" caused by mad cow disease. This article is about the epidemiology of mad cow disease. The etiology of mad cow disease, the correlation between mad cow disease and Creutzfeldt-Jakob disease and the research progress of problems to be discussed are briefly described as follows.

Epidemiological study of 1

Prevalence 1. 1

Mad cow disease (BSE) is mainly prevalent in Europe, and it has also occurred in a few Asian countries recently. There are more than 65,438,000 countries involved in BSE, and only 20 countries have BSE, including the Ministry of Health of China and the State Administration for Entry-Exit Inspection and Quarantine, which explicitly prohibit the import of products from countries infected with BSE, such as Britain, France, Germany, Ireland, Switzerland, Belgium, Luxembourg, the Netherlands, Portugal, Spain, Denmark and Finland. Italy, Liechtenstein, Austria, Poland, Slovakia, Oman, Japan and other countries. Therefore, mad cow disease has actually become a worldwide special infectious disease that is more difficult to conquer than AIDS. Canadian Agriculture Minister Vanclief announced that on May 20th, 2003, 8-year-old cows were found to have mad cow disease on a family farm in Fevieux, northern Alberta, western Canada. This news shocked the whole country of Canada, and many countries in the world announced the suspension of the import of Canadian beef. This is another heavy blow to Canada, which has not yet fully emerged from the shadow of the SARS epidemic. On the day of the news release, the relevant parties in the United States immediately announced a temporary ban on beef imports from Canada. Subsequently, Japan, Mexico, Australia, New Zealand, South Korea, China and other countries and regions also announced that they would temporarily stop importing Canadian beef. This will undoubtedly bring huge economic losses to Canada's animal husbandry and food industry.

Recently, mad cow disease has caused waves in the United States [5, 6]. It is reported that in June 5438+February, 2003, Washington State in the northwest of the United States announced that it had found 1 cow with symptoms of mad cow disease, and the case was officially diagnosed as mad cow disease on the 26th. The recently reported genetic test results show that this case of mad cow disease comes from Canada. This "mad cow" makes America fidgety. Not only is the prospect of its domestic consumer market unpredictable, but many countries have also closed their doors to American beef. As the three countries that import the most American beef, Japan, South Korea and Mexico responded quickly and announced that they would stop importing beef and related products from the United States. Other countries that have made the same decision are Singapore, Malaysia, Thailand, Russia, Ukraine, South Africa, Australia and Brazil. On the 25th, China also announced a temporary ban on the entry of cattle and related products from the United States. This is undoubtedly a heavy blow to American animal husbandry. It is estimated that the American economy may suffer huge losses of up to billions of dollars.

Mad cow disease (BSE) originated in Britain, and there were 177 962 confirmed BSE, involving 35 18 1 farms. Millions of cattle have been slaughtered and burned one after another, resulting in economic losses of nearly 10 billion dollars, making the western economic crisis worse. What is even more disturbing and intractable is the etiology and pathogenesis of mad cow disease, which is completely different from the well-known microorganisms in Shang Yun.

1.2 source of infection

From the general epidemiological point of view, the main source of infection of mad cow disease is mad cow disease. The brain and spinal cord of mad cow disease contain a large number of pathogenic factors, which are the main transmission factors; Other tissues and organs of BSE, such as liver and lymph nodes, are secondary transmission factors [6]. However, pathogens in the brain and spinal cord of sick cattle are difficult to infect healthy cattle in natural state. Only by feeding these dangerous tissues of a certain number of sick cows as feed to healthy cows can they be infected with mad cow disease. Therefore, the incidence of mad cow disease in Britain began to decline after the British government implemented the law prohibiting specific viscera from feeding cattle. This situation is somewhat similar to the spread of Kulu disease, that is, the local indigenous people have the custom of eating dead brains, so this disease can be prevalent in this area [7]. After banning the bad habit of eating human brain, Kuru disease has been basically eliminated. In addition, it has also been suggested that itchy sheep can be used as the source of infection of mad cow disease.

1.3 ways and means of transmission

There are three main modes of transmission of airborne viruses, namely vertical transmission, horizontal transmission transmission and heterogeneous transmission. In March 2000, a British baby girl named Amano, just three months old, was diagnosed as "human mad cow disease". The doctor concluded that Amanta had contracted the disease from her mother, which indicated that Nguyen virus could spread vertically through the placental barrier. The infection of Amanta ended the debate on whether mad cow disease spread vertically, and also raised new problems for the prevention and control of mad cow disease. As we all know, the placenta of scrapie is the most contagious. Sheep eating their own placenta will spread infectious factors in the pasture, making scrapie a group disease. Will mad cow disease also become a group disease? With regard to the horizontal transmission of hospital virus, academic circles have formed the knowledge that mad cow disease can cross-infect people and other animals through the food chain. Under natural circumstances, the hospital virus may pass through the digestive tract of susceptible animals, enter the mesenteric lymph nodes through the intestinal wall and proliferate, enter the nerve tissue through blood and tissue fluid, and finally enter the brain to cause various diseases. This is an extremely slow process and the main reason for the long incubation period. If people eat beef with mad cow disease or related food contaminated by Ruan virus, it will cause disease and even death. In addition, due to the strong resistance of virus removal to some disinfectants, conventional disinfection instruments may spread virus removal. At the same time, dural transplantation, corneal transplantation, cell electrode implantation and other operations will also cause the spread of the virus [8]. Studies have proved that mad cow disease factors can also infect cattle through parenteral routes. Sheep, goats, pigs, Russian monkeys, minks and mice. Sheep, goats, minks and mice can be successfully infected through the oral cavity, but the incubation period is long and the amount of infection is also large [9].

2. Etiology research

Studies have proved that the pathogen of mad cow disease is prion (PrP), an infectious factor in protein. According to the current theory, the pathogen of the disease is a kind of protein's trap structure, which has been transformed in humans and animals, mainly from α-folding to β-folding, from harmless to pathogenic, and is called "configuration transformation" or translated as change in academic field, and transformed from another kind of protein to malignant protein. That is to say, under the action of unknown factors, normal protein (PrP) is transformed into infectious air protein (PRPSC) [1].

2. 1 prion (PrP) has strong resistance to physical and chemical factors.

Under the high pressure steam conditions of 134℃ ~ 138℃ and 18 min, the virus could not be completely inactivated. The resistance to ultraviolet (wavelength 254 nm) is 40 ~ 22 times higher than that of common virus, and 10 times higher than that of potato spindle tuber virus, and the resistance to ultraviolet at 250 nm and 280 nm is stronger than that at 237 nm. Strong ability to resist ion radiation and ultrasonic wave; At 37℃, 200 ml/L formalin treatment 18 h or 3.5 ml/L formalin treatment can not completely inactivate it, but it can survive for 28 months in 100 ~ 120 mt/L formalin solution at room temperature. It has extraordinary resistance to pentanediol, propiolactone, EDTA and various nucleases (RNase and DNase). It also has a strong ability to resist ion radiation (gamma rays) and ultrasonic waves [10].

2.2 the formation of prpsc

A part of protein expressed in PrmP gene is transported from the cell to the cell through exocrine system, and anchored in detergent-resistant microdomain (DRM) rich in cholesterol, sphingolipids and glycolipids on the serosa of nerve cells through C-terminal GPI [11]. The PrPC remained in the cell partially folded into PrPSC, but at first they were only in an equilibrium state of "12", and PrPSC was stable only in the state of crystallization or aggregation. Generally, it will not agglutinate without the promotion of external PrPSC. Although some individuals will agglutinate spontaneously, this is only a small probability event. Once it enters the foreign PrPSC particles, PrPC will be irreversibly converted into PrPC. Firstly, two PrPSC molecules are axially polymerized to form antiparallel-β spiral fibrinogen dimer. Hydrophobic groups on the surface of dimer can promote the aggregation of fibrous side chains and form virus-free rod-like structures. When the dimer gradually melts, the 1 ~ 2 peptide chain can be superimposed on the periphery, thus forming a higher oligomer. Some unpolymerized PrPSC molecules are secreted into the cavity-like domain on the cell surface and enter the lymphatic-venous circulation or the nerves connected with it.

2.3 transmission route of PRPSC in cattle

The routes of oral infection and non-gastrointestinal infection are different. In the case of oral infection, the pathogen first replicates in the dendritic cells of Paye lymph nodes and mesenteric lymph nodes, and the dendritic cells transmit signals to lymphocytes through cytokines. Because Pyle lymphocytes are in direct contact with intestinal epithelium and connected with lymphatic vessels flowing into mesenteric lymph nodes, lymphocytes in abdominal cavity can enter the blood stream through capillaries, bringing pathogens to reticular lymphatic system (such as spleen and lymph nodes outside digestive tract), and then the virus replicates in dendritic cells of spleen for the second time [12]. If the infection is through abdominal cavity, the spleen is the initial replication site, followed by Payer lymph nodes, mesenteric lymph nodes and lymph nodes outside the digestive tract (such as axillary lymph nodes). In this way, PrP pathogens are distributed in gut-associated lymphoid tissue (GALT) and enter the dominant species connected with it through intestinal plexus. These nerve plexuses are connected with parasympathetic nerves in vagus nerve. In this way, PrP enters the dorsal motor nucleus of vagus nerve, solitary tract nucleus and thoracic spinal cord simultaneously along the axon of intestinal nerve. At this time, the pathogen has spread from the viscera to the central nervous system through the vagus nerve, and finally reached the replication terminal-the brain. Every time PrPSC reaches a replication site in the above-mentioned proliferation process, it will promote the transformation of PrPC of DRM[ 1 1] in nerve cells or membranes into PrPSC.

2.4 pathogenicity of prpsc

PrPSC has potential neurotoxicity, among which PrP[ 106- 126] is called neuropeptide, and this small peptide alone can also induce apoptosis of nerve cells in vitro [13]. The accumulation of PrPSC in the central nervous system, especially in the brain, can inhibit the combination of Cu2+ with SOD or other enzymes, thus reducing the antioxidant effect of nerve cells. PrPSC can also inhibit the proliferation of astrocytes induced by human exposure [14]; In addition, intracellular PrPSC may also inhibit tan-regulated tubulin polymerization, leading to changes in BU-type calcium channels, which in turn leads to cytoskeleton instability. These reasons, as well as other unknown reasons, will eventually lead to the apoptosis of nerve cells and the formation of vacuole-like structures, and then lead to various signal transduction disorders. Behavioral manifestations are autonomic dyskinesia, fear, biological clock disorder and other symptoms.

Correlation between mad cow disease and creutzfeldt-Jakob disease

After the outbreak of 1986 mad cow disease, the cases of death due to CJD in the UK have appeared continuously, and the incidence of CJD in the UK has continued to rise since 1990. Especially in recent years, a variant of Creutzfeldt-Jakob disease (vCJD) has appeared in Britain, that is, the onset age, pathological phenomena and clinical symptoms are different from those of previous CJD. The average age of variant creutzfeldt-Jakob disease is 28 years old, and the symptoms are dyskinesia. The pathological change is the appearance of amyloid, and the PrP (protein infection factor) gene has not changed. Up to now, more than 40 cases of VCJD/kloc-0 have been found in the world, mostly in Britain and Europe, and most of these people have died [1]. Variant creutzfeldt-Jakob disease occurred at the beginning of 1994, eight years after the first occurrence of mad cow disease in 1986. Can this be considered as the incubation period of mad cow disease? Since the British government announced on March 20 1996 that mad cow disease may infect people, it immediately caused panic around the world. Therefore, scientists in Britain and other countries in the world have done a lot of research on the relationship between mad cow disease and Creutzfeldt-Jakob disease, and made breakthrough progress. More and more evidences show that mad cow disease is likely to be the pathogen of new variant creutzfeldt-Jakob disease [15- 17].

3. 1 BSE is closely related to CJD.

Because mad cow disease can make many animals susceptible, scientists are urged to infect primates with mad cow disease to prove the difference of species relationship. Recently, a research team composed of British and French scientists found that macaques can be infected with spongiform encephalopathy by injecting pathological tissue of mad cow disease into their brains. By dissecting animal carcasses and comparing with patients with Creutzfeldt-Jakob disease, it is considered that mad cow disease may infect humans. This is by far the most direct evidence that mad cow disease may infect humans.

The amino acid sequence analysis of species-related PrP showed that the closer the amino acid sequence of PrPSC (gene coding protein) was to 1/3 of PrPSC of infected host, the better the infection efficiency was. Krakauer and others compared the PrP genes of cattle and humans with those of sheep, mice and monkeys, and found that there are two striking similarities in the PrP gene sequences of cattle, humans, chimpanzees and gorillas, but there are no similarities in other animals. Therefore, it can be considered that mad cow disease (BSE) in the liver of pathogen (PrPBC) is transmitted from PrPSC of scrapie to cattle across the interspecific barrier, and the formation of specific PrPBC is more likely to spread to people, which is undeniable. However, people may be infected after eating beef with mad cow disease, thus producing a new type of Crohn's disease.

At the same time, studies have shown that transgenic mice expressing human PrP gene can produce human PrPSC and develop into adult CJD after being infected with CJD. Therefore, it is also an effective method to study the relationship between Creutzfeldt-Jakob disease and mad cow disease using this transgenic mouse. Western blot and ELISA analysis showed that the expression level of transgene was positively correlated with the copy number of transgene, but negatively correlated with the latent period of disease. Probably because the primary structure of PrP determines the infection rate, and the expression level determines the synthesis rate and disease progress of PrP.

3.2 Mad cow disease can infect people and cause new Creutzfeldt-Jakob disease.

British scientists have found that people who eat beef infected with mad cow disease will develop a new type of Jakob disease, leaving chemical signs very similar to mad cow disease. Molecular markers can also provide a detection method for this fatal encephalopathy. They compared PrPSC extracted from the brains of people who died of various creutzfeldt-Jakob diseases and new creutzfeldt-Jakob diseases with each other, and with PrPSC isolated from mice infected with mad cow disease and creutzfeldt-Jakob disease. The results showed that PrPSC isolated from Creutzfeldt-Jakob disease was very similar to PrPSC isolated from mice infected with mad cow disease, but not like PrPSC isolated from mice infected with Creutzfeldt-Jakob disease. This result makes people believe that 10 young people who died of creutzfeldt-Jakob disease reported by Will and others were caused by eating beef with mad cow disease. Because 9 of them have eaten beef or beef products in the past 10 years. But none of them ate cow brains.

4 several issues that need to be discussed

The incubation period is extremely long (5-50 years), so it is difficult to find an effective detection method. At present, the most effective bacteria and virus detection methods, such as PCR and ELISA, are powerless to BSE.

Multi-organ and multi-channel infections increase the difficulty of prevention and control. At present, it is known that it can be transmitted through other routes besides respiratory tract, such as digestive tract, blood, skin and mucosa. This is why cattle (especially bone marrow, viscera, eyeballs, etc. ) and bovine serum, collagen (including medicinal capsules) are strictly controlled.

The risk assessment of bovine cosmetics, including whitening cream, lipstick, freckle cream, anti-aging cream, collagen mask and various shampoo and shower gels, especially the usual bovine placenta preparations, needs further study.

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