The Effects of HIV Mutations on the Immune System Science C.J. Stimson INTRODUCTION The topic of this paper is the human immunodeficiency virus, HIV, and whether or not mutations undergone by the virus allow it to survive in the immune system. The cost of treating all persons with AIDS in 1993 in the United States was $7.8 billion, and it is estimated that 20,000 new cases of AIDS are reported every 3 months to the CDC. This question dealing with how HIV survives in the immune system is of critical importance, not only in the search for a cure for the virus and its inevitable syndrome, AIDS (Acquired Immunodeficiency Syndrome), but also so that over 500,000 Americans already infected with the virus could be saved. This is possible because if we know that HIV survives through mutations then we might be able to come up with a type of drug to retard these mutations allowing the immune system time to expunge it before the onset of AIDS. BACKGROUND In order to be able to fully comprehend and analyze this question we must first ascertain what HIV is, how the body attempts to counter the effects of viruses in general, and how HIV infects the body. Definition HIV is the virus that causes AIDS. HIV is classified as a RNA Retrovirus.
A retrovirus uses RNA templates to produce DNA. For example, within the core of HIV is a double molecule of ribonucleic acid, RNA. When the virus invades a cell, this genetic material is replicated in the form of DNA . But, in order to do so, HIV must first be able to produce a particular enzyme that can construct a DNA molecule using an RNA template. This enzyme, called RNA-directed DNA polymerase, is also referred to as reverse transcriptase because it reverses the normal cellular process of transcription.
The DNA molecules produced by reverse transcription are then inserted into the genetic material of the host cell, where they are co-replicated with the host’s chromosomes; they are thereby distributed to all daughter cells during subsequent cell divisions. Then in one or more of these daughter cells, the virus produces RNA copies of its genetic material. These new HIV clones become covered with protein coats and leave the cell to find other host cells where they can repeat the life cycle. The Body Fights Back As viruses begin to invade the body, a few are consumed by macrophages, which seize their antigens and display them on their own surfaces. Among millions of helper T cells circulating in the bloodstream, a select few are programmed to read that antigen. Binding the macrophage, the T cell becomes activated.
Once activated, helper T cells begin to multiply. They then stimulate the multiplication of those few killer T cells and B cells that are sensitive to the invading viruses. As the number of B cells increases, helper T cells signal them to start producing antibodies. Meanwhile, some of the viruses have entered cells of the body – the only place they are able to replicate. Killer T cells will sacrifice these cells by chemically puncturing their membranes, letting the contents spill out, thus disrupting the viral replication cycle.
Antibodies then neutralize the viruses by binding directly to their surfaces, preventing them from attacking other cells. Additionally, they precipitate chemical reactions that actually destroy the infected cells. As the infection is contained, suppresser T cells halt the entire range of immune responses, preventing them from spiraling out of control. Memory T and B cells are left in the blood and lymphatic system, ready to move quickly should the same virus once again invade the body. HIVs Life Cycle In the initial stage of HIV infection, the virus colonizes helper T cells, specifically CD4+ cells, and macrophages, while replicating itself relatively unnoticed.
As the amount of the virus soars, the number of helper cells falls; macrophages die as well. The infected T cells perish as thousands of new viral particles erupt from the cell membrane. Soon, though, cytotoxic T and B lymphocytes kill many virus-infected cells and viral particles. These effects limit viral growth and allow the body an opportunity to temporarily restore its supply of helper cells to almost normal concentrations. It is at this time the virus enters its second stage. Throughout this second phase the immune system functions well, and the net concentration of measurable virus remains relatively low.
But after a period of time, the viral level rises gradually, in parallel with a decline in the helper population. These helper T and B lymphocytes are not lost because the bodys ability to produce new helper cells is impaired, but because the virus and cytotoxic cells are destroying them. This idea that HIV is not just evading the immune system but attacking and disabling it is what distinguishes HIV from other retroviruses. THE THEORIES The hypothesis in question is whether or not the mutations undergone by HIV allow it to survive in the immune system. This idea was conceived by Martin A.
Nowak, an immunologist at the University of Oxford, and his coworkers when they considered how HIV is able to avoid being detected by the immune system after it has infected CD4+ cells. The basis for this hypothesis was excogitated from the evolutionary theory and Nowaks own theory on HIV survival. Evolutionary Theory The evolutionary theory states that chance mutation in the genetic material of an individual organism sometimes yields a trait that gives the organism a survival advantage. That is, the affected individual is better able than its peers to overcome obstacles to survival and is also better able to reproduce prolifically. As time goes by, offspring that share the same trait become most abundant in the population, outcompeting other members until another individual acquires a more adaptive trait or until environmental conditions change in a way that favors different characteristics. The pressures exerted by the environment, then, determine which traits are selected for spread in a population.
Nowaks Theory on HIV Survival When Nowak considered HIVs life cycle it seemed evident that the microbe was particularly well suited to evolve away from any pressures it confronted (this idea being derived from the evolutionary theory). For example, its genetic makeup changes constantly; a high mutation rate increases the probability that some genetic change will …