Step by Step
1
Binding & fusion — gp120 binds CD4 plus a coreceptor
HIV's gp120 protein binds to the host cell's CD4 receptor plus a coreceptor (CCR5 or CXCR4), triggering fusion of the viral envelope with the host cell membrane. CCR5 antagonists (like maraviroc) and fusion inhibitors (like enfuvirtide) block this step.
Example: maraviroc blocking the CCR5 coreceptor specifically, preventing HIV from completing this initial binding step regardless of how much CD4 is available.
2
Reverse transcription — RNA converted to DNA
Reverse transcriptase, an error-prone enzyme with no proofreading ability, converts HIV's single-stranded RNA genome into double-stranded DNA. NRTIs and NNRTIs (two distinct drug classes) both target this enzyme.
Example: reverse transcriptase's lack of proofreading contributing directly to HIV's notoriously high mutation rate, since copying errors aren't corrected.
3
Integration — viral DNA inserted into the host genome
Integrase inserts the newly created viral DNA into the host cell's chromosome, establishing latency — this is exactly why HIV can never be fully cleared once integrated, only suppressed. Integrase inhibitors block this step.
Example: HIV's integrated DNA remaining hidden within a host cell's genome indefinitely, explaining why current treatment can suppress but not cure HIV infection.
4
Maturation — protease cleaves the polyprotein
Protease cleaves the Gag-Pol polyprotein into its functional individual components, a necessary final step for producing mature, infectious virions. Protease inhibitors block this step.
Example: protease inhibitors allowing new viral particles to be assembled but preventing them from maturing into infectious virions, since the necessary polyprotein cleavage never occurs.
Applied Walkthrough
1
A patient is prescribed maraviroc as part of their HIV treatment regimen, and a nursing student asks which specific step of the HIV life cycle this drug targets.
2
Ask: at which step does maraviroc act? The binding and fusion step, since maraviroc is a CCR5 antagonist, blocking the coreceptor HIV needs alongside CD4 to enter the host cell.
3
This is distinct from a protease inhibitor, which instead acts much later in the life cycle, at the maturation step, preventing the Gag-Pol polyprotein from being properly cleaved into functional viral components.
4
Understanding which life cycle step each drug class targets explains why combination antiretroviral therapy (using drugs from multiple different classes) is standard — it attacks the virus at several distinct points simultaneously.
Exam Application
Exams test whether you can sequence the four HIV life cycle steps (binding/fusion, reverse transcription, integration, maturation) and match each to its corresponding drug class (CCR5 antagonists/fusion inhibitors, NRTIs/NNRTIs, integrase inhibitors, protease inhibitors).
⚠ Common Trap
The most common trap is confusing which step establishes permanent latency. Integration (via integrase inserting viral DNA into the host chromosome) is specifically what makes HIV impossible to fully eliminate with current treatment — reverse transcription alone does not establish this permanent latency; it simply converts the genome format from RNA to DNA.
✓ Quick Self-Check
1. What does HIV's gp120 protein bind to during the first step of infection?
CD4 plus a coreceptor (CCR5 or CXCR4).
Tap to reveal / hide
2. What does reverse transcriptase do, and why is it error-prone?
Converts HIV's RNA genome into DNA; it's error-prone because it lacks proofreading ability.
Tap to reveal / hide
3. What does integrase do, and why does this step matter clinically?
Inserts viral DNA into the host chromosome, establishing latency — this is why HIV cannot be fully cured with current treatment, only suppressed.
Tap to reveal / hide
4. What does protease do during the maturation step?
Cleaves the Gag-Pol polyprotein into its functional individual components, necessary for producing mature, infectious virions.
Tap to reveal / hide
5. What drug class specifically targets the CCR5 coreceptor, and name an example drug.
CCR5 antagonists; maraviroc is the example.
Tap to reveal / hide