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HIV (Human Immunodeficient Virus) Replication Cycle - Early and Late Phase
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HIV (Human Immunodeficient Virus) Replication Cycle - Early and Late Phase
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HIV Replication Cycle (Early and Late Phase)HIV Life Cycle:
Early Phase
1. Attachment & entry
2. Reverse transcription & synthesis of DNA
3. DNA integration into host genome
Late Phase
1. RNA transcription
2. HIV polypeptides
3. Virion assembly & exit
1. HIV Attachment and Entry
1. HIV targets CD4 receptors on CD4 T helper lymphocytes. (Can also bind
macrophages, monocytes, Langerhans cells).
2. The spike proteins (on envelop) mediate membrane fusion:
gp120 (viral) binds CD4 (host)
gp41 (transmembrane component, viral) unfolds and extends the fusion peptide
CCR5 (chemokine receptor) is a coreceptor and enhances spike protein binding
3. Upon peptide binding, gp120 falls off.
4. The fusion protein contracts.
5. HIV envelop fuses with host cell membrane
6. Capsid enters the cell.
7. Capsid dissolves, leaving the RNA and viral capsid proteins in the cytoplasm.
8. Initiates early phase replication
Individuals who lack CCR5 are highly resistant to HIV infection
CCR5 is a target for Maraviroc drug = CCR5 blocker, prevents binding of HIV
, 2. HIV Reverse transcription & synthesis of DNA
The two RNA genomes are:
5’ capped
3’ polyA tailed
=Mimics the host nuclear RNA. This prevents HIV genome degradation by host.
HIV genome is reverse transcribed from RNA → DNA by reverse transcriptase (RT).
RT is encoded by the pol gene.
RT integrates HIV genome into the hosts genome for replication to occur.
RT has a high error rate (1-2 errors per copy of HIV) which leads to quasispecies within a
single infected individual.
Reverse transcriptase has 3 activities:
DNA synthesis from RNA template
o Host tRNA (from previously infected cell) is required for DNA synthesis
RNA degradation “destructive replication”
o Post-DNA synthesis, the RNA template is degraded by RNase H activity of RT
DNA-dependent DNA synthesis
o Able to switch roles of RT which allows the newly made DNA product to be
used as template to make complementary stand
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