HIV Variation Driven By Somatic Hypermutation in Immunoglobulin Variable Genes
Here is an explanation for HIV variation:
• HIV-1 infects many white cells - but particularly activated B cells in the early phase of infection setting up productive provirus in a significant fraction.
• During somatic hypermutation of the HIV-infected B cell, the SHM machinery is recruited and targets both the integrated transcriptionally active HIV-1 provirus and the endogenous immunoglobulin VDJ locus.
• The mutant B cell survivors will produce a single mutant antibody but also numerous mutated LTR bounded HIV-1 variants (some active but most inactive, even empty virions) .
Thus:
- The HIV-1 mutant population will always be a step ahead of the somatic antibody variants produced during affinity maturation.
- It may never be possible to produce an effective immunological vaccine for HIV without also controlling SHM in B cells.
HIV has evolved the ultimate immune evasion strategy. It has developed a means of diversification, as required or on demand. In this way the virus prepares itself to remain ahead of the host whilst it is also diversifying. Further, the survivors are being exposed to many new retroviral variants.
I hope this idea will stimulate efforts to take such a possible HIV strategy into account or disprove the proposal.
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