When should we regard an AIDs virus lurking in the genome of a white blood cell as dead (or at least harmless). Such proviruses are called defective, and commonly formed, because the process of reverse transcription (of RNA into DNA) is quite error prone.
Most would say an HIV1 provirus in the genome is dead if can’t reproduce and get outside the cell carrying it. Not so fast says Proc. Natl. Acad. Sci. vol. 117 pp. 3704 – 3710 ’20. They show that such defective proviruses can be transcribed into RNA and these RNAs can produce proteins (when translated).
There is some evidence for this as the Nef protein of HIV1 can be detected in cells and plasma even when HAART (Highly Active Anti Retroviral Therapy) has knocked plasma viremia down to a level of under 50 copies/milliLiter.
How could this cause trouble ? Easy. This would be chronically stimulating the immune system and in effect wearing it out.
This is very new stuff, and the fate of white cells containing replication incompetent proviruses which are still producing proteins isn’t known (but I’m sure this isn’t far off).