Structure Function And Pathogenesis Of Hiv In Humans Biology Essay

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In our ever growing and developing world that we live in today we still encounter various incurable disease and infections cause by microorganisms some that we have little understanding about. One common and also diverse type is HIV (human immunodeficiency virus), which causes the acquired immunodeficiency syndrome more universally known as AIDS. AIDS is a disease that suppresses and attacks the immune system allowing other opportunistic diseases to enter the human body. AIDS is of the biggest killers having a reported '16 million' (Madigan & Martinko 2006) cases either being infected or resulting in death. With AIDS claiming so many people already where does the knowledge and research stand in knowing what it exactly is and how to fight it?

HIV is the causative agent of AIDS and is categorised as a retrovirus, those that contain ribonucleic acid (RNA) as their genetic make-up or material. Within the category retrovirus HIV can be further sub grouped as the lentiviruses. Lentiviruses are termed "slow" viruses as they are known for the 'long time period between initial infection and the beginning of serious symptoms', because of this slow stage people may spread HIV without even knowing they are infected. There are two types of HIV known in humans, HIV-1 and HIV-2 which are genetically similar but so different at the same time. HIV-1 however causes more cases of AIDS in our world today.

There is much research and debate over the origin of AIDS and HIV, it still remains unknown. Between 1979 and 1981 AIDS was first recognized among homosexual men who showed severe symptoms of pneumonia. This brought forth the idea that something was going wrong in these homosexual males. Similar symptoms begun to rise in other population groups such as Africans, drug users and haemophiliacs to name a few. 1983 was the year that the causative agent was identified as HIV. Soon after lab tests were developed to detect and distinguish the antibodies to the virus in the serum. The test help determine that that virus was passed by bodily fluids either blood or semen and not by casual contact. This is why HIV can be passed via sexual intercourse and why protection is important in preventing the transmission of AIDS. However Bailes et al. ,2002 has found that the 'simian immunodeficiency viruses (SIVs), primate lentiviruses originated from Old World non-human primates in sub-Saharan Africa and radiated into at least six phylogenetic groups that roughly mirror the primate phylogeny' resulting in HIV-1. The viruses seem to show similarities however the chimpanzees did not show any symptoms and are unaffected by it. Dr Hahn 1999, explains that when natives were hunting and eating these chimpanzee's the disease was transferred somehow and over the years it has progressed further. Overall it is 'generally accepted that the origin of AIDS can be traced back to Africa' (Avert, 2011).

HIV lives as spherical particle, with each particle studded with spikes. This is what HIV is known for the spikes that protrude on the surface. 'A HIV particle is around 100-150 billionths of a metre in diameter' (Avert, 2011). HIV is too small to be seen by the naked eye and requires an electron microscope to assist in viewing. HIV consists of an outer coat that is known as the viral envelope. 'The viral envelope is composed of two layers of fatty molecules known as lipids', it works just like a membrane of a cell, providing protection for the virus. Throughout the viral envelope proteins from the host cell are embedded along with 72 copies of the complex proteins know as Env. The Env is what we see spiking or protruding through the surface, these spikes are made from the proteins gp120 (Docking glycoprotein) and gp41 (Transmembrane glycoprotein) and allows the virion to stick and adhere to the cell. Much research has been based around these proteins to assist in finding a vaccine and cure for the deadly virus. Gp41 or the transmembrane protein links the inside of the virus to the outside, which allows communication. The Inside of the virus is known as the core or the capsid. The capsid contains the vital components for replications; these are the 2 separate strands of Ribonucleic acid (RNA), 3 structural genes (gag,pol and env) and 6 regulatory genes (tat, rev, nef, vif, vpr, and vpu). Reverse transcriptase and Integrase are also located in the capsid, these are 2 enzymes that are highly involved in the replication of HIV are needed for the life cycle to continue. RNA are complete copies of the HIV genes used for replicating more of the virus, each strand contains a sequence that act as a switch. The LTR or long terminal repeat regions control the production of new viruses; this can be activated by either the host cell or the HIV. The structural proteins contain the information involved in making new structural proteins needed in the newly replicated virus particles which continues in the HIV life cycle. Each gene gag, pol and env has the same job but provided different end products. The regulatory proteins contain the information needed for the virus to make proteins that are essential in controlling the virus to infect a new cell, create the new copies of HIV which in turn causes the disease. Each regulatory protein plays a different role in the pathogenesis of HIV.

The pathogenesis of AIDS is relied upon the life cycle of HIV and how it is able to enter and replicate in the human body. We know HIV is transmitted via bodily fluids such as semen or blood, so what happens once it has entered the body? HIV has the ability to replicate inside the white blood cell specifically CD4+T cell, this is where the viral RNA is mixed with the human DNA and creates template for more viral RNA and proteins to be created. Within the cell viruses are assembled and released throughout the body to infect any other cells they can find. Initially the HIV needs to attach to the cell, this is done by the virus approaching a CD4+T cell. HIV is able to affect this cell as it have the necessary attachment site of CD4 on its surface, The glycoprotein's of the virus described earlier are able to lock in and interact with the 2 receptors (CD4 and co-receptor) on the cells surface. The strong attachment triggers a fusion of the cell membrane and the viral envelope, this is the merging of the cell and virus membranes that permits movement from one to the other. Inside the cell at the site of attachment the capsid protein un-coats and releases the viral RNA, reverse transcriptase, integrase and other viral proteins into the cytoplasm. Firstly the reverse transcriptase is used to copy the viral RNA into single stranded DNA; this is then used as a template to further copy it into double stranded DNA. This double stranded DNA now relocates to the nucleus along with the viral integrase enzyme. This enzyme has the ability to integrate the viral DNA within the human chromosome, fully infiltrating the host genetic information. The new viral DNA is used to produce the mRNA (building blocks for proteins) and the genomic RNA (building blocks for new viral particles). From here the viral RNA that has been copied is moved into the cytoplasm where it is then used to begin making viral proteins. Once the proteins are made along with the genomic RNA slowly shift towards the cell membrane where a new immature HIV cell is formed. This is done by the structural proteins surrounding the viral RNA forming a protein capsid core and allowing the host cell to fold its membrane around the protein forming a bud and protease is released. Protease hydrolyzes or cuts the proteins allowing the virus to bud off. The virus continues the cycle and as we know opens the body to other opportunistic infections. Overall once the virus has entered the host will experience a reduction in T cells or CD4+ lymphocytes and an increase in the virus cells resulting in a weakened immune system.

The CD4+T cells that are involved in the entry of the virus are destroyed once they have been used by the virus, the membrane of the CD4+T cells is disrupted and the cell can no longer survive. These are important to maintaining the function of our immune system, if the immune system is under attack it restricts the work the body can do to fight off other infections and diseases. 'Every day HIV destroys billions of CD4+T cells in a person infected' (NIAID 2011) it destroys of these cells quicker then we are able to create new healthy ones. A person is diagnosed with AIDS once he or she '(1) test positive for HIV or HIV antibodies and (2) has a drastically reduced T-helper lymphocyte count, or (3) has at least one of a number of opportunistic infections or atypical cancers'. (Madigan & Martinko 2006).

At this moment in time AIDS is incurable. The immune system is affected severely and is unable to bounce back after the attack and there is no vaccine to protect us from contracting HIV. The problem with HIV is that is has the ability to form a resistance to the drugs that are used to treat it. The drugs used "have been identified that delay symptoms of AIDS and can significantly prolong the life of those infected with HIV'(Madigan & Martinko 2006). Highly active antiretroviral therapy (HAART) is a strategy used to reduce the viral load of HIV infected individuals to below the detectable levels. HAART is reached by providing the infected with two or more antiretroviral drugs at the one time, this 'inhibits the development of drug resistance' (Madigan & Martinko 2006). The reason why HIV-1 is so resistant to drug therapy is the mistakes that occur during the vast reproductions. These mistakes are referred to as mutations, even DNA can experience mutations. Every generation in the replications may slightly vary from one to another meaning that drugs may only work on particular strands of HIV and not on others. The drug resistant HIV is able to continue replicating without being affected by the drug. When drug resistance is detected the drugs used to maintain the love levels of HIV in the host need to be reassessed and changed.

There are limited amount of approved drugs to treat HIV and in some countries most of these drugs are not available due to cost or approval, this reduces the chance of avoiding the drugs resistance in some countries. Madigan & Martinko (2006) outline the 5 different categories that the HIV drugs are divided into. (1) Nucleoside reverse transcriptase inhibitors; Inhibit the enzyme in the HIV known as reverse transcriptase. As we know reverse transcriptase 'is the enzyme that converts the single stranded RNA genetic information into complementary DNA'. By inhibiting this the virus is unable to replicate.(2)Non-Nucleoside reverse transcriptase inhibitor; 'Binds directly to the reverse transcriptase and disrupts the catalytic site' (3) Protease inhibitors; this binds to the active site of HIV protease and in turn inhibits the processing of the viral polypeptide and virus maturation. (4) Fusion Inhibitor; has the ability to bind to the protein gp41 and inhibits the fusion or joining of HIV to the host cell membranes. (5)Integrase Inhibitors; interfere with the integrase enzyme that is used to integrate the HIV RNA into the host DNA. All of these classes of drugs work differently and target different aspects of the life cycle however they are not as effective alone as they are together. 'Multiple drug therapy reduces the possibility that a drug-resistant virus could emerge' (Medigan & Martinko 2006), the possibility is reduced as the virus needs to become resistant to the combination of the drugs as opposed to a single drug. These five classes have been developed over different time periods, as time has progressed so has the development in drugs to effectively treat and maintain the levels of HIV in the host's body. The treatment of the person needs to be assessed constantly to ensure that the drug therapy is effectively working. Once the viral load becomes too high over '500 copies of HIV per millilitre of blood'(Madigan & Martinko 2006) the drug cocktail then needs to be reassessed and a new one needs to be delivered.

Creating a vaccine to prevent further cases of HIV seems to be impossible. As already discussed HIV is ever changing and a vaccine will have to 'provide sterilizing immunity against the circulating populations of HIV-1 as well as those yet to evolve' (Wong-Staal & Gallo 2002). This adds complication to the already long and hard struggle with the virus. There are many research program around trying to find a cure or vaccine to prevent HIV however they have had no luck. The HVTN (HIV vaccine trial network) have published that they have recently experienced a breakthrough in a vaccine that reduces the viral load. This would decrease the chances of HIV being transmitted from a HIV positive person to one without it. However they do believe a preventative HIV vaccine is still many years away and they are still in the process of answering key scientific factors first. There are ways to prevent the transmission of HIV without the use of drugs at the moment, contraception or protection. HIV is known to be sexually transmitted as it is a swapping of bodily fluids and one easy and simple way that people may neglect that can save our life is the use of a condom.

HIV affects our immune system and is the causative agent for AIDS. Many people have already lost their battle with AIDS with others still fighting in hope that a cure will arise, others are helping to design better treatment or a cure. At the moment there are copious amounts of knowledge about HIV alone but only a significantly small amount of information present on how to fight HIV. It's important to incorporate and test the knowledge we already know to find more answers. HIV is a very complex virus and explains why the research is so in depth and complex in its own way, it won't go down without a fight really. HIV is forever slightly changing making it harder to find a unique way to destroy it. Treatment needs to start instantly and can change over the course of time, it consist largely or trial and error to work out what is right for the individual are every HIV will be slightly different to the next. Imperatively HIV does not kill a person, it weakens the host immune system allowing other opportunist infections like pneumonia to enter and further destroying or destructing the host. The opportunistic infections that enter are those that the host finds difficult to fight against with a weakened system which can result in death.