Long-time readers of ERV know lots about HIV-1. You might think you dont, but you do. You know how ‘drug resistance’ works in a quasispecies. Most people dont. You know that AIDS is actually an exhausted hyperactive immune system, not a ‘weakened’ immune system. Most people dont. And you know some fun HIV-1 evolution facts, like where it came from, and what its doing now.
So I think you all will really like this Nature Reviews opinion piece about Vpu:
Vpu is not a ‘core’ retroviral gene (gag, pol, env), its an accessory gene, as is nef. Nef has lots of regulatory functions– downregulate this receptor, upregulate that receptor, Kirchhoff calls it ‘master manipulator of cellular trafficking, signal transduction and gene expression’. Its kinda like an HIV-1 wedding planner. It makes sure the flowers are delivered on time and the host cell has enough cake for everyone. Seems like it might be a dispensable gene… but if HIV-1 doesnt have it, all hell breaks loose.
But nef is a gene all HIV/SIVs have. What does this have to do with Vpu?
- Viruses that have Vpu have nef genes that cannot downregulate host cell CD3.
- Viruses that do not have Vpu, have nef genes that can downregulate CD3.
CD3 is a host cell receptor that activates the T-cell. WAAAAY too active T-cells is what leads to immune system exhaustion–> AIDS. HIV-1 has Vpu!
As a consequence of the loss of Nef-mediated down-modulation of CD3, HIV-1-infected T cells respond strongly to TCR stimulation and show marked increases in transcription of the viral genome and various cellular genes, as well as in activation-induced cell death, whereas those infected with SIVSMM or SIVAGM maintain a resting phenotype.
… this might be because an effective virus release factor permits production of a sufficient number of progeny virions owing to increased activation of virally infected T cells, despite the shortened lifetime of these T cells, or because the ability of Vpu to counteract tetherin facilitates effective virus spread in an inflammatory environment.
The fact that vpu was specifically acquired in the primate lentiviral lineage that gave rise to HIV-1 and may have allowed the emergence of primate lentiviruses that cause higher levels of inflammation and immune damage supports the hypothesis that AIDS is, at least in part, the result of an unfortunate evolutionary coincidence.
‘An unfortunate evolutionary coincidence’– the gain of Vpu and a loss of function in Nef, helped HIV-1 kill people.