HIV (Human Immunodeficiency Virus): Possible Lines of Control

This cat has gene for heterozygous normal white (CfW.cfw); a white cat would have gene for homozygous normal white (CfW,CfW). Such cats differ in form or morph

What causes the mutation of macrophage that is supposed to counter HIV?

What lines of defense are possible against the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS)?

By possible we mean whatever can be thought of. However, our list will not be exhaustive. By probable, we mean one that has been verified to work. Likewise, our list will not be exhaustive.
I have an earlier Hub “Heredity as a factor in susceptibility to HIV” that mentions that a mutation in the macrophage makes for a susceptibility to HIV.

One possible line of defense against HIV is to counter this mutation, that according to scientists is polymorphism.

“Polymorphism[1] in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph....

“Polymorphism is common in nature; it is related to biodiversity, genetic variation and adaptation; it usually functions to retain variety of form in a population living in a varied environment.[3]:126 The most common example is sexual dimorphism, which occurs in many organisms. Other examples are mimetic forms of butterflies (see mimicry), and human hemoglobin and blood types” (Wikipedia).

Genes control the morph
Let’s look into hemoglobin, the protein in the blood that carries oxygen. Normal hemoglobin (like a rounded coin) is controlled by the gene HbA. There is an abnormal hemoglobin that looks like a sickle that causes sickle cell anemia. This is controlled by the gene HbS. A person with gene HbS, HbS dies in 45 to 46 years even when given medications. The main reason is that his hemoglobin does not carry enough oxygen for use in metabolisms in his body.

Let’s look into hemoglobin in relation to malaria. A person with heterozygous normal gene (HbA,hba) is more resistant to malaria than a fellow with a homozygous normal gene (HbA,HbA). A gene consists of two alleles; one allele (HbA) may come from the father, the other allele (Hba) may come from the mother. Take note of the capital and small letters. Capital letter indicates dominance, that is, its expression is the one shown or manifested in the person.

In science of genetics, genes are designated in several ways. Hb means hemoglobin; A indicates normal. S indicates abnormal. This discussion is a little bit technical; suffice it to show that genetics is already advanced in so far as the genetics of the chromosomes in the nucleus of the cell is concerned.

There is also genetics of the mitochondria that has 37 chromosomes. In effect a person has two sets of chromosomes, one found in the nucleus and another found in the mitochondria. Genetics of the latter has not been given enough attention (Bellomo, M. The Stem Cell Divide. 2006). Chromosomes in the mitochondria are passed on only by the mother because they reside in the egg that comes into fertilization. The egg has a fluid where the mitochondria resides. The father does not carry mitochondria because his “seed” does not contain fluid that should carry them. During fertilization the nuclear chromosomes of the father (23) unites with the nuclear chromosomes of the mother (23) resulting in an embryo with 46 chromosomes. The mitochondrial chromosomes unite as well. A gene in the nucleus is designated as HbA, for example; a gene in the mitochondria is designated as mtHbA.

In the case of the mutated macrophage: what is the gene that controls the form of macrophage? There are thousands of genes of man that comprise the 46 nuclear chromosomes and 37 mitochondrial chromosomes, the heredity material. Virus has very few, 5 to 10 genes. The human genes that control macrophage must be identified. There are very few textbooks that deal on the genetics of mitochondrial chromosomes. It is easier to trace inheritance in the mitochondrial chromosomes than in nuclear chromosomes.

For example, the nuclear genes that control motor neuron disease (MND) or amyotrophic lateral sclerosis (ALS) or Lou Gehrig disease has been identified. This gene is SOD1 that controls the copper zinc superoxide dismutase. (Cu/Zn SOD). This, together with the manganese SOD, protects the mitochondria that produces energy . A mutation of SOD1 results in MND, that involves nerves that control the muscles resulting in paralysis but the brain remains intact. I have a Hub on what MND is.

Identification of the genes that when mutated results in susceptibility to HIV takes time. For example, it took 9 years to identify the genes that control heritable breast cancer, BRCA1. However, now that the project that profiles the human genome had been completed, it might be much easier to identify the genes. It will cost a lot. If done by a private firm it will cost to get examined for a mutation in macrophage. Testing for BRCA1 and BRCA2 (heritable ovarian cancer) is expensive. The Bioarray test kit may be able to see mutations in a person but may be unable yet to identify mutations in genes that control macrophage.

Cause of mutation
Assuming that the genes that control macrophage has been identified. What causes it to mutate? Is it spontaneous, that is, does it occur during meiosis? Scientists mention that the mutation is heritable, so it must be during meiosis. However, a person carrying a mutated macrophage gene does not mean that he is outrightly susceptible to HIV. Does susceptibility involve the two-hit postulate involved in cancer? For example, in BRCA1 mutation in this gene is heritable but another mutation in the same cell must occur for breast cancer to fully develop. And that is mutation in p53 gene. This is a switch that if normal, it blocks that development of breast cancer. If p53 gene is mutated, development of breast cancer proceeds (Cummings, M. Human Heredity, Principles and Issues. 2009).

The macrophage disabled
When the macrophage is mutated it may fail to recognize HIV. Such failure results in failure to mount a counter.

How is such counter mounted? The macrophage counters a microbe by plucking an antigen from the surface of the microbe and latching it on the same surface. The antigen changes the size and shape of the microbe. So changed, the microbe cannot find a channel in the cell that fits its size and shape. Thus it cannot enter the cell; therefore, fails to infect. This is how vaccination works.

Artificial vaccine
Some lessons can be learned from the feat of Sir James Black in inventing the beta blocker. This is an artificial hormone. It works by competing with adrenalin, a hormone, in hooking onto receptors of cells. When the adrenalin hooks onto a receptor it affects the work of cell, like accelerating contraction of smooth muscles. This results in angina or heart attack. Beta blocker (modified propanolol) is prescribed for a person with heart disease or hypertension. (It has a side effect of bleeding in the lungs, though).

The artificial vaccine consists of a substance or particle that latches on the surface of HIV. Its size and shape so changed, the HIV cannot enter the cell and fails to infect. I have a Hub on how to make artificial vaccine based on the killed-virus polio vaccine.

Will glycoprotein envelope work as vaccine?
The vaccine against hepatitis B virus may give some insight. Hepa B virus consists of protein coat and RNA. There are more protein coats than there are RNA. The protein coat can be separated from RNA. A gene that controls the production of protein coat had been identified and inserted into a bacteria. When this bacteria multiplies it also multiplies the protein coat; thus the bacteria is turned into a factory of protein coats in a technology called recombinant DNA in biological engineering. These coats are used as vaccines. They induce the immune system to mount a counter against hepa B virus.

HIV has a glycoprotein envelope (Lajtha, A. Handbook of Neurochemistry and Molecular Neurobiology. 2007). Does it behave like a protein coat? That is, can the glycoprotein envelope be separated from the HIV RNA? What is the gene that controls the production of glycoprotein coat? This could be inserted to a bacteria like Escherichia coli that serves as a factory of glycoprotein envelopes; these could be used as vaccines.

Environment as cause of mutation
Sporadic factors, other than meiosis, have been identified to cause mutation. Free radicals belong in sporadic factors or environmental factors.

For example, there is a form of colon cancer that is heritable (familial adenomatous polyposis) controlled by the genes adenomatous polyposis coli. I have Hubs “How heritable colon cancer develops from polyp (benign tumor)” and “Even without heritable polyp a person can develop colon cancer.” In the latter I discuss how free radicals cause mutation in adenomatous polyposis coli (APC). Free radicals and its derivatives mutate a copy of APC. This APC duplicates itself thus two copies of APC emerge. These cause the formation of adenoma, fingerlike projection, that is a forerunner of colon cancer. Five to seven more mutations in genes of the same cell promote colon cancer.

It remains to identify the free radical or derivative (hydrogen peroxide, peroxynitrite, alkoxy radical, hydroxyl radical) or their combination that causes mutation in macrophage. For example, hydroxyl radical has been identified as the most probable cause of the mutation of SOD1 in MND.

Will chelation therapy work?

Dr. Arturo V. Estuita MD, a Filipino internist and chelationist, is now treating hepa B victims with infusion chelation therapy since March 2012. So far he has treated 10 patients, Dr. Estuita told me. I have a Hub "A medical breakthrough in the control of hepatitis B by chelation therapy."

The mechanism can be as follows: The main ingredient of the chelation solution, EDTA (ethylene-diamine-tetra-acetate) binds with and removes hepa B virus. EDTA has a negative charge; HIV probably has a positive charge. The two form a ligand, a compound, owing to their charges. The chelate, combination of HIV and EDTA, is disposed off through the urine.

Will stem cell therapy work?

New entries as of December 11,2012.

A macrophage whose anti-HIV gene had been mutated may not be able to undergo apoptosis. This is programmed cell death that is a way of throwing out damaged cells. We are assuming a two-hit process in disabling macrophage. One mutated allele is inherited; the other allele is normal. (A gene consists of two alleles.) The normal allele must be mutated to result in disabled macrophage.

Stem cell therapy is a method of producing new cells, including macrophage. Some cells of the HIV victim can be extracted and grown in test tubes then infused into the AIDS victim. This involves risks and difficulty. The cells for culture must be healthy; there is a risk of culturing mutated cells. It is difficult to pick out healthy cells.

Stem cell therapy is now being used in leukemia and motor neuron disease (MND), for example. Cord blood taken upon birth and preserved in a blood bank is a sure cure for leukemia in case s/he gets afflicted when growing up. In MND, stem cell therapy has a partial success because a reservoir of free radicals ( hydroxyl radical), is produced by the body. Chelation therapy that catches free radicals and derivatives must be applied in tandem with stem cell therapy. End of new entries.

New entries as of December 13,2012

HiV attacks the macrophage when still young, called monocyte, which differentiates into macrophage. A monocyte is vulnerable to HIV (Lajtha, A. Handbook of Neurochemistry and Molecular Neurobiology. 2007). HIV enters the brain by this mode. By the time the monocyte had reached the macrophage stage the latter is already partly disabled. HIV in the brain causes dementsia. To make the problem worse, the blood-brain barrier is impenetrable by drug against HIV. In a way the blood-barrier protects the HIV; thus the brain serves as a factory and reservoir of HIV. Drugs against HIV that can pass through the blood-brain barrier must be developed, like highly active antiretroviral therapy. HAART, introduced by the United States in 1996-1998, reduced mortality of HIV dementsia victims by 60%. I have a new Hub "Dementsia as caused by HIV." End of new entries.

Whether or not the cause of mutation of the macrophage is spontaneous or free radicals takes time to find out. The above considerations can be used in coming up with various hypothesis for use as guide in medical research to develop prevention, or treatment, or cure of AIDS.

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