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The new petascale Blue Waters supercomputer at the National Center for Supercomputing Applications at the University of Illinois with this super impressive processing power has been able to simulate the largest structure ever solved - a structure of 64 million atoms - the structure of the HIV capsid . The researchers found that the HIV protein shell comprises 216 hexagons and 12 pentagons

The proteins in the hexagons and pentagons were identical but the angles through which they attached to each other were different among different regions of the structure.to achieve this tha HIV capsid would have to be inherently flexible to form such a varied structure.

By having pentagons as well as hexagons, the capsid can form a closed structure just like a phenomenon called induced acute curvature . this structure has 64 million atoms which are continuously changing (Mutating).

Schulten says that knowing more about the detailed structure of the HIV capsid will help researchers understand how it functions, and this helps drug developers work out how to disrupt those functions.

A peta-scale super computer can perform in one second the same number of instructions that all people on earth combined tall and short fat and thin black , and white can handle in about two days time !

The eventual cause ones death if HIV finds its way into our body is not that ugly monster we imagine HIV virus to be, but the beautiful HIV cone shaped capsid. .it’s in the HIV capsid that the lethal fluids are protected and ones inside the cell the capsid intelligently releases the genetic material almost miraculously into the cells with out a slightest knowledge of the security agents of our bodies .once injected the process of slow death commences .

You may need to know this processes/stages :

Step1:

The "HIV crosses the wall by exploiting the cell's processes of entry of nutrients to the cell through the its wall (cytoskeleton) . It “taps” your cell receptors on the cell wall so as to attach itself to the cell wall for entry. Ones it has touched just like a knock on the door and you hear a familiar voice of a good friend calling your first name .Gabriel! . Gabriel after hearing the sweet familiar voice will come out and opens the door. Now that the door is open the HIVcapsid is dropped inside making the end of stage one.

It may surprise know that the HIV virus is very intelligent! It doesn’t go on rampage to just attach itself to any cell it comes across but hijacks only a type called helper T-cells,killing some ,and making some act as its reservoirs for further infection .This causes T-cell numbers to drop, making the body vulnerable to disease.

Helper T-cells protect the body's immune system by arranging forces to fight off infection . Helper T-cells are in two forms ; "Virgin" cells - those that have never encountered any infection, while those that have ever encountered an infection are known as memory helper T-cells. Now the HIV is known to attack this experienced cells.

Weifeng Wang, PhD Biosciences of George Mason University HIV study's main author, explains:

"In the body, HIV is able to kill most memory helper cells. We wanted to pursue what makes the difference between memory and naive T-cells on a molecular level."

Unlike virgin helper T-cells, memory T-cells are very mobile and constantly on the go. It is this rapid mobility that seems to attract the attention of the HIV to the memory helper T cells and leaves the virgin cells that are known to be largely insensitive to HIV because their cytoskeleton is different from that of memory helper T-cells .

STAGE 2

Now that HIV is done with the first step ,the capsid now dropped finds its way into interior of the cell its ultimate destination is the nucleus .HIV capsid is injected into the host cell’s fluid interior, where it releases two copies of single-stranded RNA and associated enzymes.

STAGE 3

The third stage occurs when the HIV viral RNA is converted to DNA for entry into the host cell’s nucleus. Ones here it starts reprogramming its protein-building machinery by deliberately inserting its own genes into the cellular DNA.

At this stage a cellular enzyme called DNA-dependent protein kinase (DNA-PK) becomes ;in normal cell operations before the HIV attacks the cell this enzyme is known to help repair the double-stranded breaks in molecules that makes up DNA. But what is surprising is that ;when HIV integrates its genes into host cell DNA the role of this DNA-PK changes, it results in formation of single-stranded breaks at the insertion points!

The DNA breaks now occurring during HIV integration activates DNA-PK to triggers a signal that causes apoptosis(death) in the CD4+ T cell. A destructive role rather than a productive role it previously played all courtesy of the mystery of HIV !

So Every day in an infected person the HIV destroys billions of infection-fighting CD4+ T- cells, until the immune system is no longer able to regenerate or fight other infections.

HOW HIV DESTROYS INFECTION FIGHTING CD4+T-CELLS.

1.Direct killing of cells : It fully takes over the cells and uses their resources to make copies of itself. These copies emerge as buds that burst through the cell membrane, killing the cell in the process.

2. HIV kills the host cell directly just by exhausting the cell resources.

3. When the host cell machinery becomes grossly distorted from being used to make virus copies, this can trigger a process known as programmed cell death or apoptosis

While this processes are happening the HIV is mutating very fast making Memory cell soldiers not able to recognize it, rendering our immune system defenseless against it. In addition to this, the virus kills many memory helper cells.

Its in this way that makes HIV a tough target for drugs.

POSSIBLE MEDICAL INTERVENTIONS ;

a).: Schulten explains how the HIV capsid has to perform two opposing functions. It has to remain intact to protect its genetic material, but it also has to be able to release it in a timely manner once inside the host cell so it can replicate. so inventing a medicine which can infiltrate the HIV capsid while its releasing the genetic material of course- this has to take place with really accurate timing-not too quick not too slow.The timing of the opening of the capsid is essential for the degree of virulence of the virus. This is where we could perhaps best interfere with HIV infection," he adds.

b) Researchers found that certain regions of the proteins interact with one another in a way that is "critical for capsid assembly and stability, and for viral infectivity.

It is equally certain that HIV protein shell comprises 216 hexagons and 12 pentagons .The proteins in the hexagons and pentagons were identical but the angles through which they attached to each other were different among different regions of the structure.

So attempting to alter this angles artificially with an aim of inhibiting the opening of HIV capsid to release its lethal genetic” bomb “ would make it have a free ride in the cell without causing any harm .

c) From George Mason University research findings ;Medical professionals may be able to treat HIV-infected people in the early stages of infection by giving them drugs that block those early steps in virus replication that occur up to and including DNA-PK activation as well as receptor attachment .

And not only might this stop the virus being able to copy itself, but it could also preserve enough CD4+ T cells to keep the immune system able to fight infection.

D) Possible ways on how to eliminate resting HIV-infected cells which act as reservoirs for HIV could be sought since a scientific explanation on how they are formed has been cracked by researchers of George Mason University

e) Other scientists suggest that ;The new strategy should aim at a cellular target that HIV depends on to exist, and then shutting it down . For example, if the cell was a house and the virus needed electricity to live in the house say here in "lagos ", researchers could target electricity. The tricky part will be shutting it down without impacting healthy cells along with it.

F) Target and eliminate the cellular ingredient which HIV depends to exist and wreck havoc on our T-cells.

G) Attempting to reverse the hyper sensitivity and mobility of memory helper T-cells. So that its cytoskeleton doesn’t respond to a signal from HIV just like its counter part the virgin T-cells .

H) Cancer cells and HIV cells share the love of migration, meaning cancer drugs that slow down cancer migration could potentially be used to treat HIV. The George Mason University team are headed this direction in looking towards existing drugs, especially those used to treat cancer to equally make HIV immobile so that its rate of infecting new cells is reduced

O De Mabior

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