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Description
An estimated.two-thirds of the 36.7 million people infected with.the Human immunodeficiency.virus (HIV), resideon the African.continent 1. Once infection.has occurred, HIV destroys.the hosts CD4+ immune.cells, leading toacquired.immunodeficiency syndrome (AIDS) 2. .HIV/AIDS is wide.spread throughout.Sub-Saharan Africa andexacerbates various.socioeconomic issues 3. South Africa has.some of the highest prevalence.of HIV/AIDS.in theworld, with an.estimated 7 million people.living with HIV 4. .An estimated 115 000.HIV-related deaths occurred inSouth Africa in 2018, .emphasizing the.need for HIV research.in Sub-Saharan.countries 4.The HIV-1 virus.consists of two copies.of non-covalently.linked, positive.sense, single-stranded.RNA molecules 5.This is enclosed.by a p24 viral.protein.conical capsid, situated.within a.viral envelope. .The viral envelope isderived from the.host cell membrane and.contains viral.glycoproteins; such.as gp120.and gp41, which.areimbedded.in the viral.envelope 2,6,7. .Once HIV-1 exposure.occurs, .the virus migrates.to CD4+ immune.cells. Thisoccurs.due to the.affinity of the HIV-1 viral.envelope.gp120/gp41 complex.for CD4 antigen.receptors on thesurface of host.CD4+ immune cells 2,6. Once.the gp120 subunit.of the viral envelope.interacts with a CD.antigenreceptor, co-receptor binding.takes place 2,7. The co-receptor.binding results in conformation.changes in the HIV-1 envelope, .leading to the exposure.of the gp41 hydrophobic.domain, allowing.fusion of the.envelope with.thecellular.membrane and the.subsequent delivery.of the viral core.into the cytoplasm 2. The.uncoating of the.viralcore exposes.Reverse transcriptase, a HIV.enzyme, to deoxynucleotide.triphosphates (dNTP's), resulting inreverse transcription.and proviral DNA synthesis 2. After reverse.transcription is completed, .the formation.of acomplex, consisting of.viral and cellular components is.formed, known as the viral pre-integration.complex. This istransported to the.cell's nucleus where the.HIV-1 enzyme, Integrase, catalyses.the integration of the viral.genomewith the human.DNA 2,7. This maintains the.viral DNA.in the infected host cell and allows.transcription, thus thecell can express viral.mRNA and viral RNA. Once.transcription is initiated, the necessary viral.constituents moveto the inside of the plasma.membrane and assemble to form an.immature HIV-1 virus 2. The newly.formedimmature virus buds.off from the cell and releases.protease to break down large.HIV-1 protein chains. .Thesebroken down HIV protein.chains, combine to form.a mature HIV-1 virus 2.The viral life.cycle, discussed above (shown in Figure 1.1), can be.subdivided into seven.distinct stages, namelybinding; fusion; reverse.transcription; integration; replication; .virus assembly/production; and.budding. The HIV-1lifecyclexpresents various.potential opportunities for.therapeutic intervention.and six distinctclasses ofantiretrovirals (ARVs) havexbeen developed 2.
