FIG. 13.

Augmentation of HIV-1 multidrug resistance via human sequence transduction. Shown is a schematic overview of the mechanism by which an HIV-1 strain gained enhanced resistance to multiple RT inhibitors during replication in a Japanese child. (A) The top line shows a preinsertion sequence of the HIV-1 strain replicating in the boy's parents and in the child prior to the acquisition of drug resistance; the lower line indicates the sequence of the multidrug-resistant isolate. Blue shading indicates the region of a 30/31 match to human chromosome (chr.) 17. (B) Proposed mechanism for the acquisition of human sequences. (i) Establishment of a provirus upstream of the transduced sequences and generation of a readthrough RNA. (ii) Nonhomologous recombination between viral and human sequences. (iii) Further point mutagenesis during replication in the patient to generate the sequences observed for the patient (314).