Hiv Term paper

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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.

HIV s 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

body s 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 Nowak s 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.

Nowak s Theory on HIV Survival

When Nowak considered HIV s 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 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...

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