Figure 7.

Proposed model for the role of PCID2/TREX2 in HIV-1 gene expression during viral latency

(A) In latent cells, PCID2/TREX2 is present at the HIV-1 LTR transcription start site (TSS) and blocks HIV-1 gene expression and promotes viral latency at two distinct levels: transcription initiation and RNA alternative splicing.

(B) Upon PCID2-DSS1-MCM3AP downregulation, LTR-driven transcription is re-started. In addition, absence of PCID2-DSS1-MCM3AP leads to increased splicing of intron-containing unspliced (US) viral RNA and accumulation of completely spliced (CS) HIV-1 RNA. Because PCID2 facilitates export of mRNPs as part of the TREX2 complex via the NXF1 pathway, its downregulation leads to nuclear retention of CS HIV-1 vRNA.