EAN: 9783384219756

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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.

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