HIV-1 might has selenoprotein coded and benign CVB3 might change suddenly into vicious viruses and subsequently induce myocardial necrosis. These study results at a gene level has already attracted people¡¯s attention to the relationship between selenium and viral diseases, especially AIDS. Taking selenium 200 ug a day is conductive to resist cancer and make the outbreak and death rate of cancer declined by 50%. The study on the role of selenium on the AIDS and viral diseases, especially in respect of the resistance of virus transcription has undergone for many years. Compared with the study on selenium and cancer, the study on the relationship between selenium and viral diseases has always been neglected by the major scholars and clinical doctors. This paper has analyzed and summarized the results of the study on selenium and viral diseases, especially on AIDS in resent years. The results show selenium is closely related with AIDS and has a practical value in the control of AIDS. In China the alarm bell has rung for the prevention of AIDS: In China, 1/3 territory are lacking selenium, several hundred million people are taking deficient selenium, the environmental pollution are leading to the constant decline of selenium level in the substance chain. Are these encouraging the trend of continuous increase of AIDS? We should pay great attention to it, and strengthen the study on selenium and its application as well as AIDS.1.Facts
1.1Fact: Selenium is a trace element essential to human bodies, selenium cysteine is the active center of selenium-containing enzymes, and the main functions of selenium are as follows:
- Strengthen antioxidant defense. In the selenoproteins, the glutathion peroxidase family has the functions to remove free radicals and impede fat peroxidation, and is an important member in the defense system of the organism.
- Adjust thyroid hormone. The transfer of T4 to T3 in the thyroid gland depends on deiodinase. The deiodinase is a selenium-containing enzyme.
- Participate in the formation of sperms. The content of selenium in sperms is the highest, the formation and stability of sperms depend on the selenium and male sterility has something to do with the selenium.
- Adjust the immunity of organism. Immunity, especially the cell immunity is significantly influenced by selenium. As immunity is related to AIDS, the relation between selenium and immunity will be discussed later.
1.2 Fact: Sufficient selenium is essential to keep the immune system normal, especially to T cells.During the culture of cells, the supplement of selenium can strengthen the poisonous action of cells to kill and wound T cells, promote the antigen and mitogen to induce the multiplication of T cells. On the contrary, lack of selenium will result in the decrease of immunologic function. The number of CD4=T cells of animals, old people and patients with infectious diseases varies with the selenium level in plasma. When T lymphocytes are initiated, the mRNA of Sps2 genes of selenium cysteine is adjusted up, indicating that T cells are in need of selenoproteins.
1.3 Fact: Selenium can strength the action of interleukin2 (IL-2)Il-2 sees a bright prospect in application for treating AIDS, but its side effects are strong. Selenium can adjust up the IL-2 accepter genes and improve the efficacy of IL-2. These indicate the supplement of selenium can reduce the dosage and decrease the side effect of IL-2.
1.4 Among the HIV infected persons, the decrease of selenium is synchronized with the decrease of the number of T cells, and the selenium level in the organism has become an important index in predicting the survival conditions of HIV patients.
More than 20 theses have reported that the selenium level has lowered with the HIV infected persons including children and old people with or without symptoms. The research institutions in different cities and different countries, such as New York, California, Florida, Italy, Spain, Germany, France and Belgium, all have found the similar result. After infected with HIV, the selenium will decrease. The traditional explanation is that this phenomenon is brought about by malnutrition and malabsorption. However, many scholars hold that behind this phenomenon lies still deeper reasons. Among the patients with AIDS, whether with or without diarrhea and protein malabsorption, there is a principle that the contents of selenium and glutathion peroxidase in the plasma are in direct proportion with the number of gross lymphocyte. This indicates that the lowering of selenium in the organism should not be fully contributed to malabsorption of the intestines and stomach. Some scholars also reported that before the appearance of consumption symptoms, namely at the primary stage of illness, selenium might also flow away. The selenium in the urine could reflect directly the selenium intake state. But the contents of selenium in urine? discharged by the crowd with HIV-1 positive were similar to that of negative, indicating there was no difference in the intake of selenium for the two categories of people. Other studies have confirmed that the decline of selenium in patients with AIDS is not induced by malabsorption, and the state of illness and survival of AIDS patients can be predicted with the contents of selenium. In the course of cell culture, there is no problem with malabsorption. The cells infected by HIV-1 are likely to result in the decrease of glutathion peroxidases. All these further reject the explanation about malnutrition and malabsorption.
Tiny molecules of selenium compound can restrain the HIV-1 outside of the body.
- Oxidation adversity can activate the reproduction of HIV-1. The supplement of tiny molecular selenium compound can strengthen the activity of glutathion peroxidases and reduce the activation of HIV-1. It can be seen that the selenium can inhibit: (1) the cell toxicity of viruses; (2) the viral activation induced by hydrogen peroxides; (3) the activation of NF-KB (can activate HIV-1); (4) the activation of HIV-1 BY tumor necrosins.
- ?Tiny molecular selenium compound, at the level of micromole concentration, can inhibit HIV-1.
- ?Inorganic selenium compound can inhibit reverse transcription viruses and inhibit ox leukovirus outside of he body.
- The results produced from selenium menonine are contrary to the above. Selenium menonine can induce the expression of endogenous reverse transcription viruses. However, if the selenium menonine has a concentration 100-1000 times higher than that adopted in the above research or higher than the physiological concentration of human body, the results will bear no physiological significance.
1.6 Fact: AIDS is always accompanied the symptoms of hypothyrea or decreased T3 content.
Among the patients with AIDS, exist a wide spread phenomenon of lacking thyroid hormone and lowering T3 level. The transformation from T4 to T3 depends on selenium-containing deiodinases, and the decline of T3 level reflects the decline of selenium level. At present, growing hormone for human is always used to treat the consumption symptom of AIDS, but it is through deiodinases that the growing hormonecan can promote the transformation from T4 to T3. Therefore, sufficient selenium can strengthen the activity of deiodinases and make the treatment more effective.
1.7 Fact: a lot of sighs show oxidation adversity will stimulate the reproduction of HIV, whereas some antioxidants can inhibit the reproduction of HIV. This indicates that patients with AIDS have defects in antioxidation. Selenium is one of the key antioxidant elements, and lack of selenium in the body of AIDS patients will induce an oxidation adversity and stimulate the production of HIV. All of these can be improved by selenium supplement.
1.8 Fact: the selenium content in the semen is the highest in human body. And HIV has a preference for parasitism in the semen. This indicates the HIV needs selenium.
1.9 Fact: evidence shows lack of selenium in human being and animals also has something to do with other viral diseases.
- Hepatitis B: the encoded reverse transcriptases of hepatitis B are very similar to the inverse transcription viruses. In Qidong County of Jiangsu Province, hepatitis B and liver cancer induced by hepatitis B were prevailing for some time and have been significantly lowered down through large scale selenium supplement experiences for 5 years.
- Keshan disease: Keshan disease is a typical selenium-lacking disease. In Keshan County of Heilongjiang Province, the soil and crops are short of selenium, and this is the main pathogenic factor. The Keshan disease is featured by its outbreak in a partial area and at a specific season. Some researchers? presumed that a certain viral cofactors have participated, but afterward, CVs were identified out in the heart of the dead. In case of selenium lacking, the benign CVB3 changed suddenly into vicious CVs, the toxicity of which even can lead to myocardial necrosis of chmices.
- Animal viruses: in animal and agricultural documents, there are many examples about viral diseases induced by lack of selenium to animals.
2.Hypothesis: are there common foundations in the phenomenon observed above?
The antitoxic effect of selenium might come from its multi-layer biochemical action. The facts listed above regarding the close relation between selenium and AIDS demonstrate there is a special relationship between selenium and AIDS, and supplement of selenium might be an essential and beneficial measure, especially for some patients. Now the question is why. The reasons are summarized in the following paragraphs to help explain the above-mentioned observation results.
1.10 Selenium, HIV and AIDS: viral selenoprotein theory
Will Taloy et al have, by application of computer analysis method, predicted that in the RNA structure, the protein code area might contain a new reading frame, indicating that in the HIV, there are several new selenium-containing protein genes which can be encoded, and have identified out the special RNA organs needed for the expression of these new genes. These new genes might be the foundation for selenium to adjust the HIV.
The decline of selenium contents is not only a factor that induces the attack of AIDS, it might also involve the mechanism with which HIV induces AIDS. In the HIV infected cells, the selenium decline and the potential viral encoded selenoproteins induced by viruses can help us explain why AIDS is sensitive to oxidation adversity. Different observation results are highly in conformity with the theory.
What might make people feel puzzled is that if viruses need selenium, why the virus reproduction can be increased when the selenium is lacking? Would not the selenium supplement ¡°feed¡± the viruses while it inhibit them?
Taking a classical example to help us understand this relation of reciprocity, arginine is the amino acid essential to the synthesis of viral proteins, when the arginine is lacking in the cell substrate, it might induce the expression of inverse transcription viruses, this indicates the reproduction of viruses might be activated because lack of the element needed by the viruses. This belongs to a suppressing mechanism and this mechanism is not rare in viruses, such as tryptophan. In the response the HIV and CVB3 make to the lack of selenium, a mechanism similar to that the defect of arginine results in viral reproduction might has been adopted. On the othe4r hand, because glutathion peroxidase genes have been detected in some kinds of viruses (such as HIV-1 and hepatitis B), the virus glutathion peroxidases might also have a suppressing effect on the virus reproduction. It has been known that the oxidation adversity (such as hydrogen peroxides) can activate the reproduction of HIV and other viruses, whereas the virus glutathion peroxidases can relieve the oxidation adversity, so as to reduce the activation of viruses. The encoded glutathion peroxidases of the viruses can also help defend the attack on the infectious cells from free radicals of immune system and increase the survival of viral particles in the blood flow and outside of cells, because after the shell-wrapped viruses leave their host cells, they can not use the antioxidant defense to safeguard themselves, and if there are not such enzymes, the viruses will be attacked by peroxides and generate film fatty peroxidation.
1.11 Latent selenoproteins, CVB3, Zaire Ebola viruses, poxviruses and hepatitis B viruses in other viruses
Study has been conducted on other viruses with computer analysis method and has produced similar results as that of HIV-1. In the study, CVB3 is used as a model, and there is reliable theoretical foundation that shows this kind of viruses contains genes that use selenium, one of them might be the gene module of shortened glutathion peroxidases.
Zaire Ebola viruses are high pathogenic viruses (inducing hyperpyrexia and hemorrhagic fever). In these viruses are hidden protein genes and special gene structure that expresses the selenoproteins. In these selenoproteins, there are 16 UGA selenium cysteine codens, namely, each selenoprotein needs 16 selenium atoms. This indicates that after infected by Zaire Ebola viruses, the viruses might take a large quantity of selenium. In other words, because different selenoproteins contain different number of selenium atoms, the selenium lost within several dozen days after infected by Zaire Ebola viruses amounts to that lost within 10 years after infected by HIV. This can explain the mechanism of quick deadliness of Zaire bola viruses. In the Reston Zaire Ebola viruses that are not pathogenic, there is no selenoprotein gene. It can be seen there is a sharp contrast between the two kinds of Zaire Ebola viruses in terms of selenoproteins and pathogenicity. Besides, selenium is related to the pathology of Zaire Ebola viruses, which are highly infectious to the rich selenium organs such as blood and liver. After infected by Ebola viruses, the blood would coagulate, resulting in the rupture of capillary and blood heat. It is known that lack of selenium is related to the formation of thrombus, depth lack of selenium for animals would lead to bleeding, and blood coagulation can be controlled with sufficient selenium.
Up to now we have not studied the selenium state and fatty peroxides in the patients with Zaire Ebola viruses. However, relevant clinical study results show they have something do with the lack of selenium. The scholars in our country have succeeded in relieving with sodium selenite the hemorrhagic fever symptom (similar to that of Zaire Ebola virus disease) induced by Hantaan virus infection. For 80 cases, taking orally 900 ug of selenium (sodium selenite) continuously for 9 days, the death rate is 7%, whereas the death rate for those who have not taken is 38%, with the total death rate declined 80%. At present, effective medicines are not available to treat hemorrhagic fever. With selenium as a treatment agent at a dosage 4-5 times the dosage for health care, a significant effect can be achieved in a short period, manifesting significance of selenium to the disease. Although the study did not involved Ebola viruses, the above mechanism that is common to many hemorrhagic fever viruses and the dosage of selenium are likely to be success in treating other hemorrhagic fever viruses, including Zaire Ebola viruses.
Poxvirus is a DNA virus, which contains selenoprotein genes and has a 76% homology with the amino acid series of glutathion peroxidases. These genes express the activity of glutathion peroxidases in the human keratinocytes, and therefore, it can be confirmed that these viruses can encode selenoproteins.Through comparison between glutathion peroxidase module of the genes of HIV-1 viruses and hepatitis C viruses, it have been found they have much in common, and selenoprotein modules are likely available in many RNA and DNA viruses.
1.12 Local disease in Africa: Kaposi caruncles
The areas of volcanic rock soil in Africa, such as the gorge area in east Africa, are of selenium lacking areas, and the Kaposi caruncles are the local disease. Evidently, both the outbreak of Kaposi caruncles in Africa and that of keshan disease in our country are featured by the lack of selenium and with viruses as cofactors.
Significance of Prevention and control
Before the appearance of the theory on viruses and selenoproteins, there were already many evidences that support selenium supplement is conductive to HIV infected persons. Even though the theory on viruses and selenoproteins is proved wrong in the future, the above-mentioned facts can not be denied. Therefore, it is reasonable to recommend the supplement of selenium to the HIV infected persons and use selenium to prevent the quick spread of AIDS in accordance with the study materials available at present. This kind of recommendations is also appeared in some publications about the prevention of AIDS with selenium, and in some simple clinic tests, the effect of selenium on AIDS symptoms has been observed.
For healthy persons, it is safe and effective to take 200 ug of selenium a day; for HIV infected persons, it is reasonable to take 400 ug a day if they are indeed suffering from respiratory disturbance and for AIDS patients who show distinctive signs of lacking selenium, the method adopted by some clinical study for selenium supplement is to take 800 ug a day first within a few weeks to increase the selenium content in the blood and then adjusted to 400 ug a day.
Owing to the narrow range between the dosages of selenium for nutrition and toxicity, some disputes might occur over he dosage of selenium. In fact, the concerns occurred over the toxicity of selenium has been exaggerated. Taking selenium 1000 ug a day does not shows any signs of so called acute toxicity. In some areas, people take selenium 600-700 ug a day for a long time, but have no signs of toxicity. In North Greenland and Enshi of China, the intakes of selenium of many people are always as high as 1000 ug a day. Therefore, for the carrier of HIV viruses, it is safe to take 400 ug per day. In addition, the symptoms, such as significant smell of garlic in the respiration and sweat, metal taste in the mouth, unusual fall-off of hairs and nails, of chronic selenium toxicity can be easily detected, and after reduction of the intake, the symptoms will automatically disappeared.
Supplement of selenium is not only effective in prevention of cancer but also has potential function in the treatment of some virus diseases, including some acute and deadly diseases. As observed, the pharmacological dosage of selenium, eg 900 ug a day, is effective in saving the life of patients with virus hemorrhagic fever, and it is worthwhile exploring deeply the prevention and control of AIDS with selenium.
The lack of selenium bears a relation to the occurrence of AIDS as well as the breakout and death rate of many kinds of infectious diseases (including AIDS). Due to the industrial pollution, acid rain and the reaction between selenium and a large number of sulfur dioxides, plus the modern planting method, there is a trend toward continuous lowering of selenium in the foodstuff chains. In the past 20 years, the intake of selenium of the people in Britain, a highly developed country, has declined nearly 50%, approaching the level of selenium lacking areas. Our country has witnessed a high-speed economic development, but also accompanied by serious industrial pollution and high discharge of sulfur dioxides. This situation is not optimistic, and the AIDS in our country has a tendency to expand. This tendency, if not reversed in time, will become a ¡°national disaster¡±. Under his background, adequate supplement of selenium to the crowd facing high dangers will be perhaps the most simple, inexpensive and effective way to the prevention and control of AIDS.
The theory on virus selenoproteins is supported by a lot of evidences (although many of them are in the terms of theory). It has been confirmed that poxviruses contain selenoproteins, the HIV, hepatitis B and keshan viruses have significant sighs of containing selenoproteins, and for the Zaire Ebola viruses, there are enough internal evidences to indicate the adjusting function of selenium on the pathopoiesis of these viruses. A great number of facts have shown the lack of selenium is the high dangerous factor of the development of HIV illness and the death of HIV patients. Reliable evidences are available that illustrate the selenium compounds are able to inhibit the activation of HIV induced by the oxidation adversity. Although these results are not sufficient to prove that the selenium is able to inhibit HIV through the mechanism of virus selenoproteins, they are in conformity with the prediction of this theory.
A wide and deep study on the effect of selenium on the prevention and control of AIDS has been conducted and is recognized in the world, the prevention and control of viral diseases, such as AIDS, have achieved primary results and the study on the prevention and control of AIDS with selenium should be strengthened.
Abstracted from ¡°Medicine World¡±, P53-55, issue 10, 2004