The AIDS Virus:
Its Origins, Effects, Transmission and Genetics

Clark Brean
1994 Woodrow Wilson Biology Institute

"If the Biological Warfare Division were to design a virus, I think they would have a hard time coming up with a better one."
Comment of a genetics student after first learning of the AIDS virus.

This paper will attempt to provide specific, current information on the HTLV-III virus. Please realize that as work is continuing in this area information changes on an almost daily basis. Also, statistics quoted in this paper will obviously soon become obsolete. It falls to the presenter of this information to stay current with the latest developments.

Origins

HTLV-III: The "AIDS" Virus

The AIDS virus seems to have originated in central Africa during the early 1950's. This information has been compiled from epidemiological studies and is backed up by studies that have looked at banked blood study samples from the area. The exact location of origin of the disease is not known. The virus appears to be a mutated virus from the African green monkey (Cercopitcecum aethiops), which harbors the Simian T-Lymphotropic Virus-III (STLV-III). This particular virus infects the monkey but seems to produce no pathogenic effects.

Apparently, the virus then mutated to a form that would infect humans: the Human T-Lymphocyte Virus-I (HTLV-I). The mode of infection of this virus was probably through bites and scratches delivered from the monkey as they are often kept as pets. The virus underwent further mutations, producing LAL-2 and SBL. The latter two variants are capable of human infection and cause a mild immune deficiency disease.

Sometime in the early 1950's the virus "completed" the mutation process and produced its HTLV-III form, the AIDS virus. Though further mutations of this virus continue today, they have not been sufficient to produce a "new" type.

HTLV-IV: The Other "AIDS" Virus

HTLV-IV seems to have originated in West Africa in a similar time and in a similar manner to HTLV-III. HTLV-IV contains the same complement of genes, attacks and kills the same human cells, and acts by the same mechanisms. The disease it causes produces symptoms and effects that are indistinguishable from HTLV-III.

Though these two viri seem so similar, they are in reality different. They have evolved separately, in separate geographical areas and genetic testing shows only a 45% homology. However, the viri are similar enough that the tat gene of one will activate the other.

In the final analysis, HTLV-IV is considered a different virus, but treated and tested for along with HTLV-III. At present, its rate of infection is so low in the U. S. that it is not considered a problem organism. As such, this report will concentrate on HTLV-III but make comments where appropriate on HTLV-IV. It should be noted that HTLV-IV is the major virus in many locations in Africa and cannot be ignored for this reason.

Spread of the Disease

Epidemiological evidence indicates that the HTLV-III virus remained localized in central Africa until the early 1970's. It was then spread to Haiti where it became well-established by the late 1970's. By 1980 the virus had entered the U. S. and Europe.

In 1981 the Centers for Disease Control and Prevention, Atlanta, identified the first fatal cases of AIDS, and properly identified it as such. The disease was originally noted because many of its victims suffered from a hitherto rare form of cancer known as Kaposi's sarcoma. This form of cancer produces tumors of the blood vessels of the skin and internal organs. Normally this condition only appeared in elderly Italian and Jewish men. Suddenly it was appearing in unusual numbers in white Anglo-Saxon Protestant homosexual males. This unusual occurrence originally clued the CDC into the fact that something unusual was going on.

In 1983, while working with an electron microscope, a French worker named Montagnier at the Pasteur Institute first identified the cause of the disease as the AIDS virus. One year later, this work was confirmed directly from case isolation by workers in the U. S. By 1985 a commercial blood test for the presence of the AIDS virus antibody became available. This allowed the Red Cross and hospitals to test their blood supplies and "guarantee" that people would receive uncontaminated blood transfusions.

It should be pointed out that this test is not a 100% guarantee. A few forms of the virus will not be detected by the present antibody test (commonly ELISA, though some organizations run others as well) though constant efforts are being made to change and update it. Also remember that it may take up to six months for the human body to produce antibodies for the AIDS virus, and it is these antibodies that the blood test searches for. Finally, it should be pointed out that the blood test does not confirm the presence of the AIDS virus, it simply tests for the presence of antibodies. It is this fact that led researchers to mistakenly believe some babies were born with HTLV-III and later eradicated it from their systems.

In 1986 the HTLV-IV virus was isolated and identified as a separate entity by Montagnier in France. 1987 saw the identification of the HTLV-V virus and more recently the HTLV-VI virus is claimed. These last two viri are questionable as they have only been isolated from one or two patients and the differentiations between them and pre-existing viri are not entirely clear.

General Information

"AIDS raises a host of thorny issues, the scientific being perhaps the easiest to manage. With testing, insurance, employment, housing and medical care, society must come to grips with protecting the civil rights of individuals while at the same time ensuring the public health and national well-being."
Editorial comment of Chemistry and Engineering News

The AIDS Complex

The AIDS complex is probably best visualized in the form of a pyramid. In this diagram, the bottom "Well" category represents individuals who harbor the virus but do not yet show any symptoms of the disease. They will test seropositive for the AIDS antibody and represent the greatest number of individuals not yet affected by the disease.

The second level, labeled PGL, represents individuals affected with Persistent Generalized Lymphodomathy. Basically, this is the stage of the disease whose most notable characteristic is that of swollen lymph glands.

The third level, ARC, represents individuals affected with AIDS-Related Complex. The fourth level represents individuals affected with true, full-blown AIDS disease. This level contains by far the smallest number of individuals.

Diagnostic Characteristics

Full-blown AIDS victims exhibit most of the following characteristics:

Kaposi sarcomas which show up as purple blotches and mush-like deep bruises on the body surface. This bruised appearance is due to deep capillary rupturing.
Oral carcinomas that include skin cancers in the mouth and rectum. This condition is commonly misidentified as "thrush."
B-cell lymphomas.
Gammaglobulin count elevation.
Helper T-Cell fusion and inactivation. The general number of T-Cells in circulation will fall and become very low. It should be pointed out that this low cell number is not enough to cause the AIDS disease as by this time there are insufficient viri in circulation to cause the massive system damage associated with the condition. (1x10 5 peripheral blood cells making the virus...a very low number when compared to a normal viral attack. This means that most of the viri are in the latent phase.)
Monocytes and macrophages are infected by the virus. The viral infection does not kill these cells outright, but uses these cells as a reservoir to bud within and spread the disease throughout the body. Up to 70% of diagnosed cases show infection of the spleen, skin, lining of the abdomen and lining of the lungs which were probably infected from these reservoir cells.
Death of the stem cells of the bone marrow.
The viri are picked up and incorporated into the nerve and brain cells. This is termed "AIDS cephalopathy" and may lead to AIDS-dementia complex which better than 2/3 of all AIDS sufferers eventually exhibit. Nerve and brain invasion may cause major abnormalities of cognition, motor and/or behavior. The early stage of infection elicit loss of mentation precision and motor control. The patient often experiences growing apathy, tremors, gait unsteadiness, slowing of the reflexes and loss of hand/eye coordination. The intermediate phase is characterized by intellectual impairment, slow muscle response and deep apathy. Speech becomes slurred. Finally, mutism will occur. The person will experience severe dementia, limb weakness and inconstancy.
- The virus mainly invades the subcortical structures of the brain: the central white matter, basal ganglia, thalamus, brain stem and spinal cord. It causes actual brain atrophy with lesions in the nervous tissues which lead to loss of white brain matter throughout the course of the disease.
- The viri are incorporated into and causes increases in the number of glial cells (astrocytes) around the nerves. They are also found in the oligodendrocyte where they secrete factors which are toxic to the nerves. Finally, they are incorporated into the capillary endothelium and disrupt the blood/brain barrier.
This viral infection opens the way for the opportunistic infection of other organisms which results from the weakening of the immune system. Often, Pheumocystis carinii pneumonaea infections overwhelm the body. (This protozoan is a normal inhabitant of the body and is usually considered "harmless.")
Dry cough.
Weight loss.
Shortness of breath.
Individuals are considered to be in the ARC stage of the disease when they exhibit the following symptoms:
Unexplained, often high, fevers.
Night sweats.
Weight loss.
Chronic cough.
Diarrhea.
Unexplained lymphadenopathy (lymph node swelling).
Fatigue.
Skin rash.
Lower infection resistance than normal.

The PGL stage is characterized by the general lymph nodes swellings and "Well" individuals show no symptoms but are a reservoir of the virus.

Population Effects/Prognosis

The best statistical estimates place the number of people infected with the HTLV-III virus at about 1,000,000+ (CDC data, 9-93), or 1 in 250 people in the U. S. Estimates of this number do vary with some placing the figure as low as 750,000 and some as high as 3,000,000. Middle-of-the-road estimates place the infection rate at about 375 people a week.

Estimates also vary as to how many of these infected individuals will eventually develop AIDS. Conservative experts place this number at about 30% for development within the next 5 years. This figure ranges as high as 80%.

From 1981 to Sept. 1993, 339,250 people have been clinically diagnosed as having full blown AIDS; 293,642 men, 40,706 women and 4,906 who where 13 and under. Of this total, 204,390 had died and 134,860 were still alive. The above statistics contain 2,963 adults and 202 pediatrics who contracted the disease as hemophiliacs. The 13-19 year old age group reported 1,412 cases of AIDS and the 20-24 year old age group reported 12,712 cases.

The CDC predicted a 75% increase in AIDS cases for 1993 and actually saw a rise of 111%; an increase of 103,500 individuals. The CDC estimates that 1:100 males would test positive for the HTLV-III virus and that 1:800 females would similarly render a positive test. The only groups of individuals that did not increase their numbers of AIDS cases were the homosexual and bisexual males. The greatest increase in the number of reported AIDS cases were in heterosexual females and in teens.

In some populations of Africans, the infection rate is 30% of the sexually active adults. The sex ratio of infection for these populations is 1:1. The infection sex ratio in the U. S. and Europe is about 8 males to 1 female, but the female infection numbers are growing. It should be pointed out that presently the cases of infection among heterosexuals is increasing slightly faster than among those now considered to be "at risk."

Estimates of the numbers of people infected world wide are about 15,000,000. Over 130 countries have confirmed one or more cases within their country. It should be pointed out that some countries will not give out statistical information on AIDS and that some will not admit that AIDS exists within their borders.

Individual Effects/Prognosis

Once full-blown AIDS has been diagnosed in the individual, the mean life expectancy is 4 years. The mean incubation period from initial infection to clinical AIDS is 8 years. Thus, from infection to death is about a 12 year period of time. The virus may also lie dormant for up to 10 years before beginning this progression. Most experts do feel that the development of this disease is inevitable, but some hold out hope that a few cases will never progress to AIDS.

Studies show that 95+% of patients progress to a more virulent form of the disease. Once progression from the "Well" stage has begun, there are no known cases of regression. A person may stabilize at some further stage for a while and even though this pause may last for a long period of time, it is just a pause.

Once disease progression has begun, the HTLV-III virus seems to gradually and continually mutate. Each mutation seems to be slightly more cytopathic and can infect more cell types. Originally it was believed that multiple strains infected the body and were serially expressed. Studies have established that only a single strain infects the body and that mutations produce the differing strains.

Proven Disease Transmission Modes

All forms of sexual contact - male/male, male/female, female/female - have been shown to transmit the HTLV-III virus. Furthermore, all forms of sex - vaginal, oral and anal - transmit the virus. The following statistics may be helpful:

The chance of transmitting the virus is 2-4% per contact.
The chance of transmission if the female is infected and the male is uninfected is 5-10% per contact.
The chance of transmission per contact is 22% for a female if her male partner is bisexual.
The chance of transmission is 21% per contact if either partner is a hemophiliac.
The chance of transmission is 42% for a female if her sexual partner is an intravenous drug user.
The chance of transmission is 31% if your partner has had 100+ sexual contacts.

Again, remember these are statistical values for the "average" situation and person. The values themselves will change with time and situation. As an example, the further along in the AIDS disease cycle the sexual partner is, the higher the chance of transmission. Non-circumcision increases the rate of transmission. Some individuals are infected after the first exposure; some never seem to be infected.

Direct blood-to-blood contact of any kind has been shown to transmit the virus. This contact may be in the form of intravenous drug users sharing needles, lab technicians accidentally sticking themselves with contaminated needles, contaminated blood entering cuts or any other form where contaminated blood contacts normal circulating blood.

White blood cell transference is another method of transmission. White blood cells contain the HTLV-III viri; some shielded within the cells, some as incorporated viri within the cellular DNA.

Plasma transfusions may transmit the virus. This is true only if the plasma contains the blood platelets.

The virus may cross the placental membrane and infect an unborn child. About 50% of babies born to HTLV-III infected mothers will soon become AIDS victims. It should be pointed out that if a child is tested at birth, it will be positive for the antibody test due to the mother's antibodies. These antibodies disappear about 6 months after birth and the child begins to manufacture its own antibodies. At this point it may be tested to determine whether it has the disease or not.

The virus may be transmitted during parturition by the birthing fluids. For this reason, most babies delivered to mothers suffering from HTLV-III infection are delivered by Cesarean section. The virus may be transmitted through the mother's milk. For this reason, children of HTLV-III infected mothers should not breast feed. Children infected by milk, or who are infected by the birthing process or in the womb, have a mean life expectancy of 2 years.

Health workers have become infected by contact with other body fluids of infected individuals. Some workers were infected through conditions like eczema and some received contact through the eyes or mouth. Again, body fluids from the infected individual may include tears, saliva, urine, vomitus, etc. Remember, all body secretions contain the virus.

Non-transmission Situations

The following list contains ways in which the virus definitely is not spread:

Casual skin contact
Coughs
Sneezes
Toilet seats
Casual kissing
Swimming pools
Giving blood
Cloths worn by, utensils used by, telephones used by an infected individual
Blood-sucking parasites

Because of the high incidence of HTLV-III infection in Belle Glade, Florida (second highest rate/10,000 individuals in the U. S.), and the location of this town on the edge of a large swamp, it was originally feared that ticks, fleas, chiggers, mosquitoes, etc. could spread the disease. (Indeed a retrovirus in sheep - the visa virus - is spread by ticks.) French workers have further shown that the HTLV-III virus may be taken up in the blood meal of mosquitoes and even survive in their gut for 2 days. Further studies have put these fears to rest and have shown that the HTLV-III virus cannot be spread this way. Continuing study of Belle Glade, Florida showed that they had an unusually high incidence of IV drug use, a high promiscuity rate, and a tremendous amount of consanguineous activity.

The HTLV-III virus itself is very fragile and will die soon after exposure to air. It is easily killed by normal household-strength cleaners and bleaches.

Continue to Part II

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The AIDS Virus: Its Origins, Effects, Transmission and Genetics