Parasitizing the Parasite; mobilization competent vector targeting modulation of HIV-1

Mobilization competent vector mediated suppression and excision of HIV-1.

(A) Conditionally replicating vectors are generated containing small ncRNA 362, shown to direct TGS to HIV by targeting epigenetic complexes to the NF-kB site in the HIV-1 LTR (Suzuki et al., 2008; Suzuki, 2005; Turner et al., 2012; Turner et al., 2009). These vectors also contain a recently engineered humanized version of the T. Thermophila pDD1pV5 protein, which excises genomic DNA in an shRNA directed manner and the MPA drug selectable gene IMPDH2.

(B) When HIV infected cells are transduced with these vectors, the vectors integrate and

(C) express shRNA (362) and Pdd1pV5 which can

(D) target integrated proviral HIV and direct both transcriptional gene silencing and Pdd1pV5 mediated gene excision of the LTR of HIV.

(E) The result of this targeting is excision of the NF-kB locus and compaction/transcriptional gene silencing of the integrated virus.

(F) The MPA selection also allows for mobilization of the conditionally replicating vectors resulting in three different viral variants those that contain virus, vector, or vector and virus and can thus spread to new cells resulting ultimately in the spread of the mobilization competent vector and it’s anti-HIV properties to neighboring viral infected cells.

Kevin Morris Lab - Figure 4