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HIV stands for Human Immunodeficiency virus, when this virus is at its most progressive stage it is known as Acquired Immune Deficiency Syndrome (AIDS). HIV belongs to the Retroviridae family. The genome of this virus is constituted of a single strand of RNA encapsulated in an HIV Capsid protein that forms the core shell of the virus. Moreover, the virus possesses a lipid bilayer composed of surface proteins and transmembrane proteins. Intracellularly beneath the lipid bilayer there is a matrix protein p17 followed by the conical capsid p24 that most commonly have the shape of a cone as seen in electron microscopes, also where the nucleic acid-binding protein and integrase are found bound to the RNA. (Seitz and für Impfstoffe und biomedizinische Arzneimittel, 2019).
HIV Anti-retroviral therapy (ART) refers to the multiple combinations or a single dose of HIV suppressant drugs that impede the progression of the viral infection. (Who.int, 2019). The anti-retroviral drugs have evolved from being a monotherapy with the administration of a single drug to a therapy that nowadays combines diverse types of drugs for a more effective response, nevertheless, complete eradication is not possible. Currently, 17 different drugs being utilised for treatment. (Volberding, P.A. and Deeks, S.G, 2010).
HIV travels through the bloodstream and with other body fluids and infects particularly T helper lymphocytes. (Nucleus Medical Media, 2013). The life cycle of HIV life cycle involves the following steps of binding, fusion, reverse transcription, integration, replication, assembly, and budding. During the first stage, a mature HIVs surface antigen binds to a CD4+ T cell surface receptor and the receptor CCR5 or CXCR4. Then, the enveloped virus fuses into the helper T cell. After, HIV reverse transcriptase enzymes serve as catalysts during HIV RNAs transcription into another RNA. During the integration step, the virus then takes over the T cells reproductive system and produces infectious particles named virions that carry the nucleic acid genome. The viruss structure progresses as a result of the proteolytic cleavage step of assembling in which the binding polypeptide chains. Once it is matured, it leaves the body and travels to infect and kill other cells.
During the binding step, the inhibitory drug utilised is Maraviroc, it impedes the binding of CCR5 to a HIVs antigen. In the fusion stage, it is the enfuvirtide that is used as it blocks the fusion of the virus into the healthy T cell. Next, the reverse transcription step has the most possibilities for inhibitory drugs by using nucleoside analogues and non-nucleoside reverse transcriptase inhibitors such as Tenofovir, Integrase Inhibitors, Abacavir, Lamivudine, Emtricitabine, Efavirenz and Nevirapine, all of these drugs will affect the nucleic acids to inhibit transcription thus inhibiting the creation of more viruses. In the integration step, Raltegravir and other integrase inhibitors are utilised to impedes the integration of the HIV RNA into the T cells genome. Finally, during the last step, the proteolytic cleavage can be inhibited by the following drugs, Atazanavir, Darunavir and Lopinavir which inhibit the proteins from cleaving to create a new mature virus.
HIV does not have a cure due to there is a small probability that a T cell with a genome that possesses instructions to produce HIV viruses can remain only dormant and it can be triggered to begin replicating HIV viruses at any moment leading to the continuation of the infection. (TedEd, 2019)
The HIV life cycle stage of budding where the virion (immature virus leaves the host cell) crosses the plasma membrane while it forms its lipid layer to mature. Budding is induced by the Endosomal Sorting Complexes Required for Transport (ESCRT). These molecules have their cycle in which they assemble and disassemble to function, to carry out this action they utilise a vacuolar protein sorting AAA-ATPase. ESCRT cannot be targeted as it is taken from the host T cells being utilised during cellular activities that are crucial such as the multivesicular body sorting pathway that regulates the cells surface receptors signalling. (Ahmed et al., 2019). The genome for that codes for these receptors could be cut from HIV, preventing it from maturing and being released to infect other healthy lymphocytes, virions are not infectious only when they mature. However, useful target proteins would be the HIV receptor Gag, this protein antigen is responsible for recruiting ESCRT proteins. (Sundquist and Krausslich, 2012).
Nonetheless, a side effect would be the possibilities that the drug could affect healthy cells receptors and the limitation is that both possible drugs would need to be combined with other types of drugs so that if the drug is inaccurate there is still another manner of inhibiting the life cycle of HIV.
Alternatively, Vpu accessory protein is utilised to promote the release of mature virions. (Janvier et al., 2011). Although, this would not be as effective since the T cell can burst and the virions can be realised and can infect other lymphocytes.
References
- Who.int. (2019). WHO | Antiretroviral therapy. [online] Available at: https://www.who.int/hiv/topics/treatment/art/en/ [Accessed 13 Oct. 2019].
- Seitz, R. and für Impfstoffe und biomedizinische Arzneimittel, B. (2019). Human Immunodeficiency Virus (HIV). Transfusion Medicine and Hemotherapy, [online] 43(3), pp.203-222. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4924471/ [Accessed 14 Oct. 2019].
- Nucleus Medical Media (2013). Medical Animation: HIV and AIDS. [image] Available at: https://www.youtube.com/watch?v=ng22Ucr33aw [Accessed 15 Oct. 2019].
- Volberding, P.A. and Deeks, S.G. (2010). Antiretroviral therapy and management of HIV infection. [online] Science Direct. Available at: https://www-sciencedirect-com.wwwproxy1.library.unsw.edu.au/science/article/pii/S0140673610606769 [Accessed 2019 Oct. 14AD].
- TedEd (2019). Why its so hard to cure HIV/AIDS – Janet Iwasa. [image] Available at: https://ed.ted.com/lessons/why-it-s-so-hard-to-cure-hiv-aids-janet-iwasa#review [Accessed 14 Oct. 2019].
- Ahmed, I., Akram, Z., Iqbal, H. and Munn, A. (2019). The regulation of Endosomal Sorting Complex Required for Transport and accessory proteins in multivesicular body sorting and enveloped viral budding – An overview. International Journal of Biological Macromolecules, [online] 127, pp.1-11. Available at: https://www.sciencedirect.com/science/article/pii/S0141813018358380 [Accessed 14 Oct. 2019].
- Sundquist, W. and Krausslich, H. (2012). HIV-1 Assembly, Budding, and Maturation. Cold Spring Harbor Perspectives in Medicine, [online] 2(7). Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385941/ [Accessed 14 Oct. 2019].
- Janvier, K., Pelchen-Matthews, A., Renaud, J., Caillet, M., Marsh, M. and Berlioz-Torrent, C. (2011). The ESCRT-0 Component HRS is Required for HIV-1 Vpu-Mediated BST-2/Tetherin Down-Regulation. PLOS. [online] Available at: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1001265 [Accessed 14 Oct. 2019].
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