.. give rise to an advantageous trait. This great genetic variability stems from a property of the viral enzyme reverse transcriptase. As stated above, in a cell, HIV uses reverse transcriptase to copy its RNA genome into double-strand DNA. The virus mutates rapidly during this process because reverse transcriptase is rather error prone.
It has been estimated that each time the enzyme copies RNA into DNA, the new DNA on average differs from that of the previous generation in one site. This pattern makes HIV one of the most variable viruses known. HIVs high replication rate further increases the odds that a mutation useful to the virus will arise. To fully appreciate the extent of HIV multiplication, look at the numbers published on it; a billion new viral particles are produced in an infected patient each day, and in the absence of immune activity, the viral population would on average double every two days. With the knowledge of HIVs great evolutionary potential in mind, Nowak and his colleagues conceived a scenario they thought could explain how the virus resists complete eradication and thus causes AIDS, usually after a long time span. Their proposal assumed that constant mutation in viral genes would lead to continuous production of viral variants able to evade the immune defenses operating at any given time. Those variants would emerge when genetic mutations led to changes in the structure of viral peptides recognized by the immune system.
Frequently such changes exert no effect on immune activities, but sometimes they can cause a peptide to become invisible to the bodys defenses. The affected viral particles, bearing fewer recognizable peptides, would then become more difficult for the immune system to detect. The Model Using the theory that he had developed on the survival of HIV, along with the evolutionary theory, Nowak devised a model to simulate the dynamics and growth of the virus. The equations that formed the heart of the model reflected features that Nowak and his colleagues thought were important in the progression of HIV infection: the virus impairs immune function mainly by causing the death of CD4+ helper T cells, and higher levels of virus result in more T cell death. Also, the virus continuously produces escape mutants that avoid to some degree the current immunologic attack, and these mutants spread in the viral population.
After awhile, the immune system finds the mutants efficiently, causing their population to shrink. The simulation managed to reproduce the typically long delay between infection by HIV and the eventual sharp rise in viral levels in the body. It also provided an explanation for why the cycle of escape and repression does not go on indefinitely but culminates in uncontrolled viral replication, the almost complete loss of the helper T cell population and the onset of AIDS. After the immune system becomes more active, survival becomes more complicated for HIV. It is no longer enough to replicate freely; the virus also has to be able to ward off immune attacks.
Now is when Nowak predicts that selection pressure will produce increasing diversity in peptides recognized by immune forces. Once the defensive system has collapsed and is no longer an obstacle to viral survival, the pressure to diversify evaporates. In patients with AIDS, we would again anticipate selection for the fastest-growing variants and a decrease in viral diversity. Long-term studies involving a small number of patients have confirmed some of the modeling predictions. These investigations, conducted by several researchers–including Andrew J.
Leigh Brown of the University of Edinburgh, et al.–tracked the evolution of the so-called V3 segment of a protein in the outer envelop of HIV for several years. V3 is a major target for antibodies and is highly variable. As the computer simulation predicted, viral samples obtained within a few weeks after patients become infected were alike in the V3 region. But during subsequent years, the region diversified, thus causing a rapid increase in the amount of V3 variants and a progressive decrease in the CD4+ cell count. The model presented by Nowak is extremely difficult to verify with clinical tests alone, largely because the diversified interactions between the virus and the immune system are impossible to monitor in detail. Consequently, Nowak turned to a computer simulation in which an initially homogeneous viral population evolved in response to immunologic pressure.
He reasoned that if the mathematical model produced the known patterns of HIV progression, he could conclude the evolutionary scenario had some merit. To verify his model, he turned to the experiments done on the V3 protein segment in HIV. These experiments demonstrated that the peptides were mutating and that these mutations were leading to a decline in helper lymphocytes. CONCLUSION Before we begin to answer the question that this paper is investigating, an evaluation of our primary experiment source is necessary, this being a publication of Nowaks model. Upon evaluation of this source, a problem is exposed, this being that because there was no experiment performed to substantiate this model, we have no idea if the modeling predictions are true.
Although there were previous non-directly related experiments ( i.e., V3 experiment) that Nowak referred to to rationalize his model there was never an experiment done solely based on the model. Because the V3 findings were in accord with the findings of Nowaks model, we can assume that the model has some merit. This absence of an experiment is what leads to the boundaries that one encounters when experimenting with HIV mutations. These boundaries being that because HIV replicates and mutates non-linearly, it is impossible to chronicle all its viral dynamics scrupulously. The lack of experimental data based on Nowaks model along with the inadequacy of experiments dealing with HIV mutations leads to the conclusion that at present, there is no answer to this question.
Although, other questions have been exposed, including: does the virus mutate at random or is it systematic? And how does the virus know where to mutate in order to continue surviving undetected? These are all questions that must first be answered before we even begin to try to determine if viral mutations are what allows HIV to survive in the immune system.