Broad Range Of Viruses That Exist Today Biology Essay

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The broad range of viruses that exist today is incredible. As we learn more about one particular virus it seems that a new one appears with qualities that have adapted to today's environment. For the pre-existing viruses it is important that we learn as much as possible about them so we can utilize this knowledge to create ways of curing and preventing ones that are similar to it. HIV is one of the puzzling viruses that exist within our society. To begin to understand it we have to become familiar with the virus's composition, life cycle, diseases it may cause, its impact on the public, and the different treatments for it.

Human immunodeficiency virus (HIV), which is classified as a Baltimore 6 virus, is a single stranded positive RNA virus (Parilla 2010). An individual viral particle consists of two pieces of RNA that is enclosed by a capsid. The capsid is conical (cone) in shape and is composed of oligometric subunits that come together to form protomers. These units form capsomere which have a 3-dimensional makeup. All of the viruses' nucleic acid is protected within this enclosure. The formation of capsid is accomplished with a core protein known as p24 which is considered a capsid protein (CA) that is encoded by the gag gene (Wills et al.). Levels of this protein are often tested for when trying to determine the progression of HIV in the host. The HIV genome consist of 10,000 base pairs and 9 open frames that code for 15 different proteins (Parilla 2010). There are three major genes that code for the different proteins of the HIV genome. The first of the genes is the gag gene and it codes for the gag protein which are important for the structural components of the particle (Morikawa 1999). These components include the matrix (MA), capsid (CA), nucleocapsid (NC) and p6 (Parilla 2010). These particular structures play a role in stabilizing the viral RNA and preventing it from being disrupted or even digested. The gag gene is unique because in the absence of reverse transcriptase, envelop glycoprotein or genomic RNA it is the only gene from the virus that is needed for formation of the particle and budding (Wills et al). Pol is the second gene of the HIV genome which encodes for enzymatic proteins which included: protease, reverse transcriptase, and integrase (Morikawa 1999). Proteases are the enzymes that are responsible for breaking down proteins by cleaving them at certain areas. By cutting these proteins it leads to maturation so they will now be able to fully function and infect other non-infected cells. This enzyme increases the amount of new cells that can be infected by the virus by creating functioning proteins. Reverse transcriptase is a RNA-dependent DNA polymerase that transcribes single stranded RNA of the virus into double stranded DNA (Parilla 2010). The function of this enzyme is important because it creates the viral DNA that that will be integrated and replicated ("Reverse Transcrition"2006). HIV, being a retrovirus, is not normal viruses because it starts with RNA and then is transcribed into DNA by reverse transcriptase; hence the name "reverse" transcriptase. Integration is accomplished by the enzyme integrase. This enzyme is able to take the DNA that was transcribed by reverse transcriptase and integrate it into the cellular DNA; which is vital to the replication of the viral DNA (Parilla 2010). The third gene of HIV's genome is ENV gene which encodes for the viral envelope protein. Gp120 and gp 41 are the two glycolproteins that serve as receptors on the surface of the virus. The ENV gene codes for gp160; which is the precursor for both gp 120 and gp41 (Parilla 2010). Gp120 binds to the CD4 receptor on other target host cells, typically the helper T-cell. When this bond occurs it activates the gp41 which is initially embedded within the envelope of the virus. This additional activation aids as the virus fuses with the host cell. This leads to the entry of the virus into the host and starts its reproduction phase.

The reproduction of HIV begins with the attachment of the viral particle to the host cell. As previously explained, on the surface of HIV are the two receptors gp120 and gp41. The first one to bind to the target cell is the gp120. This particular receptor finds a CD4 receptor to bind to and afterwards it leads to the activation of gp140. The cellular co-receptor, CCR5, is present on a range of cells that are able to get infected with HIV; these include T-cells and macrophages (Co-Receptors: CCR5 2003). CCR5, in most cases, is needed by NSI strains (strains that are most common in early infection) for infection (Co-Receptors: CCR5 2003). CXCR4 is a chemokine receptor that is found mainly on CD4 cells. These particular co-receptors, referred to as SI strands, are more aggressive and are usually associated with accelerated progression of the disease (Esbjornsson et al.). In some instances, without one of these co-receptors on the host's cell, HIV is unable to infect the cell. Once the viral particle is attached to the receptors and co-receptors it enters the cell through the process called cellular fusion. With the attachment of gp120 and the coreceptors, a conformational change occurs with exposes the gp41 receptors. This change leaves gp41 in the active form. By inserting a hydrophobic fusion peptide, the gp41 reels the cellular membrane closer (Blacklow et al.). Fusion then occurs but the complete detailed is not known as of now. One inside the cell the particle uncoats due to pH levels or acidification. This results in the release of viral RNA and reverse transcriptase into the cytoplasm of the host cell (Parilla 2010). As explained in these notes, viral reverse transcriptase is then allowed to start transcribing viral RNA into DNA in the cytoplasm. Once the viral DNA is made, the enzyme integrase integrates the viral DNA into the genome of the cell. Transcription, which requires host transcription factors, can then take place and is accomplished by host DNA-dependent RNA polymerase (Parilla 2010). As stated in the notes, sometimes the mRNA may not leave the nucleus so it becomes dormant. Once transcription is done, the mRNA is exported to the cytoplasm where translation is accomplished by the host's ribosomes. The newly made positive strand of RNA is then cut in order to render core proteins and reverse transcriptase. The core proteins assemble at the cell membrane and once it beings to pinch off the precursor protein draws two strands in and then cuts it self free (Parilla 2010). Once the precursors are cleaved the proteins undergo maturation and are ready to infect other cells; which is part of the primary infection.

Pathogenesis of HIV starts with the primary infection and goes in an acute infection. During this time, symptoms are mild and include fevers, malaise, and swollen lymph nodes (Parilla 2010). This phase in the acute infection is often referred to as the "window period" which is used to describe the period of time between the initial infection of HIV and the production of antibodies (HIV testing 2010). While in the acute infection stage, billions of viruses are made per day and is considered the most infectious time. Most of the virus is cleared with the work of the cell mediated immunity and humoral immunity but the other portion of the virus dwell in the lymph & nervous system (Parilla 2010). Clinical latency follows and this is the period in which the anti-HIV antibody count is at its highest because the virus in not floating around in the blood. Instead, it is in somewhat of a dormant period in the lymph nodes. When the HIV mutates it becomes active and pathogenic so as a result CD4 cells start to decline dramatically ("Different stages of HIV infection"2009). At this point the amount of T helper cells that are lost can't be adequately replaced. This leads to the failure of the immune system which opens the door for the symptoms to develop and for opportunistic infections to occur. The immune system is so weak and damaged at that point HIV progresses to AIDS. During this stage a wide range of infections can enter the body little or no resistance from the immune system. A staging system was created, that was based on clinical symptoms, in order to help with diagnosis and treatment of the virus ("Different stages of HIV infection"2009). As explained in the article, clinical stage I is usually asymptomatic so there won't be much symptoms besides swollen lymph nodes. It goes on to describe the clinical stage II the symptoms. These symptoms are more noticeable and include: less than 10% weight loss, respiratory tract infections, and Muco-cutanaceous manifestations (Parilla 2010). As the virus begins to progress over 10% body weight is loss, persistent fever, pulmonary tuberculosis, unexplained chronic diarrhea for longer than a month, and severe bacterial infections are all symptoms that start to appear ("Different stages of HIV infection"2009). This indicates that the infection has reached clinical stage III. The article also gives some major symptom that used to identify clinical stage IV and they include: HIV wasting syndrome, Kaposi sarcoma, chronic isosporiasis, recurrent server bacterial pneumonia, and chronic herpes simplex infection. By the time the infected person reaches this stage nothing can really be done for them. HIV is not curable so treatment is mainly supportive.

Unfortunately there aren't any drugs that can clear this infection or any vaccines that will prevent a person from getting infected with it. But there are treatments that are being used to slow down the replication of the virus. HAART (Highly-active anti-retroviral therapy) is one of the treatments that is being administered to HIV patients. This particular treatment is a cocktail of different types of drugs that target specific parts of the virus' life cycle. The drugs are used in different combinations and could include: Nucleoside RT inhibitors, non-nucleoside RT inhibitors, fusion inhibitors, protease inhibitors, intergrase inhibitors, maturation inhibitors, and immune based drugs (Parilla 2010). None of the drugs will destroy the virus instead they onlyt reduce the amount of active viruses. For the people with virus that do no seek supportive treatment are they are likely to experience symptoms earlier due to the progression of the HIV. The ones who receive treatment can possibly prevent it from progressing to AIDS. There is no current vaccine and the production of one is a steady challenge. As stated in Parilla's 2010 notes, there are problems that are associated with creating a HIV vaccine. The first problem is that the vaccine only limits the spread of the virus and doesn't block the initial infection. Another problem is that the HIV is steadily mutating and evolving so it's hard to construct a vaccine that will constantly adjust to theses changes. The third problem is that there is not a good animal model that can be used for the comparison of humans; human subjects can't be used because it would be unethical. The fourth reason is that clinical trial can often be misleading because of the complex characteristics of the virus. There are some vaccines that have been created in the past decade that have had some success. RV144 is clinical trial that was done in Thailand that tested more that 16,000 enrolled adults (Parilla 2010). As explained in the notes, it was based around two vaccines used together which was called "Prime-boost". The first one was the "Prime" (ALVAC HIV vaccine) and it was delivered in four doses and it consisted of genetically engineered forms of ENV, GAG, PRO in canary pox .The notes go on to explain the second part of the vaccine. The "Boost"(AIDSVAX/E), was administered in two doses and was a recombinant of gp120; which alter this receptor of the particles surface . HIV can be transmitted through sex (contact), products that come to contact with blood (vector) and from mother to child birth and even breast feeding (vertical)(Parilla 2010). In order to prevent from acquiring this virus, safe sex should be practiced, blood to blood transfer should be avoided, taking anti-HIV drugs during pregnancy, and by males getting circumcised (Parilla 2010).

This virus does discriminate between certain types of people but prone to infect the people who do not take cautious in their practices. Demographically, certain area of Africa, especially South Africa, are at extremely high rate of infected individuals ("Global demographics of HIV infection" 2009). These cases are most likely to cultural practices, unprotected sex, and vectors like mosquitoes. Other areas in Asia are also on the rise for the percentage of people infected with the virus. These groups of people are at a higher risk of spreading the disease more easily within their society. This contributes to the larger scale of infections when more and more people are introduced to it.

HIV is a unique virus that possesses a genome that is difficult to understand. Its reproduction capabilities and ability to undergo mutations and still operate are aspects that a vital when seeking a treatment or cure. A critical phase that must be recognized and stopped earlier is the integration of the viral DNA into the host's genome. As more is learned about the life cycle of this virus the information obtained can also help in curing it and possibly other retroviruses that aren't as deadly but are just as prevalent.

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