How does HIV mutate to prevent immunity and still maintain infectivity via the CD4 receptor?

Jul 27, 2020
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HIV invades white blood cells using the trimeric envelope complex (gp160 spike) on the HIV viral envelope, which binds to CD4 receptors, facilitating fusion of the two membranes and entry of the viral RNA genome into host cells. Yet it seemingly must mutate this very protein in order to evade elimination by an antibody response. How can this be accomplished and still maintain high affinity for the CD4 receptor? Is the gp160 spike so large and complex that mutations can occur with enough frequency to allow sufficiently infective virions to be produced which evade immune detection, thereby allowing for its continuous replication despite attempts by the host to eliminate it by repeated antibody responses?
 
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Jul 27, 2020
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Or/and does the virus have the mechanism to mutate as it needs?
It seems likely that there is an inherent, random inaccuracy in RNA polymerase (and/or reverse transcriptase) which permits some level of mutation. After all, many viruses do not undergo such mutations, allowing for life-long vaccinations. It does however seem to be common in many retroviruses (RNA genome) since the same issue also impacts flu, common cold, and other viruses like SARS-CoV-2, etc.

Such random mutations clearly would offer an advantage to the virus in order to escape elimination by the immune system, providing a selective pressure for such a trait to evolve.
 
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Jul 27, 2020
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You mean it self-mediates. Now why would it do that?
If by "it self-mediates" you mean it controls its own mutation and infectivity. That would be correct, but only by default. Due to an inherent error in the mechanism of proof-reading of RNA polymerase, which produces a large number of the virus's genomes before they are packaged inside the infected cell.

HIV is produced in considerable numbers with mutations in many places. This is very common in many retroviruses. It would seem that the error rate is high with HIV and likely produces a lot of inactive virions. But it still produces enough active ones that allow it to continue to infect other cells and remain viable, but at a greatly reduced level. That may be why it takes so long to prove fatal. Perhaps it destroys your immune system in slow motion, and by extreme stealth.
 

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