NIH Research Festival
The host factor LEDGF/p75 interacts with HIV-1 integrase and causes integration to favor active genes. Recently, we published the genes favored by HIV-1 integration have high numbers of introns and that LEDGF/p75 interacts with splicing factors and is required for integration in highly spliced genes. LEDGF/p75 and HRP2 contain domains that bind chromatin and integrase. In mouse embryonic fibroblasts (MEFs) lacking LEDGF/p75, expression of human HRP2 restores the integration preference for active genes. To test whether this activity of HRP2 also restores the preference for highly spliced genes, we analyzed published integration data. We found in MEFs lacking LEDGF/p75, human HRP2 does promote integration in highly spliced genes. This raises the possibility that like LEDGF/p75, HRP2 may have a role in splicing. Capsid (CA) mutation N74D shifts integration from gene dense to gene poor regions. By analyzing published integration we found N74D reduced HIV-1’s preference for highly spliced genes. To test the role of CA in the distribution of integration within transcription units (TUs), we divided the refseq annotated TUs into 15 equal parts and tabulated the inserts in each segment. We found integration in WT MEFs, HIV-1 has a preference for the 5’ end of TUs. With N74D, integration is evenly distributed across TUs. In MEFs lacking LEDGF/p75 there is a strong spike of integration in the first segment of TUs, and this pattern was unaffected by N74D. This suggests that LEDGF/p75 and N74D function independently.
Scientific Focus Area: Virology
This page was last updated on Friday, March 26, 2021