CPSF6 and HIV-1 CA HARVARD UNIVERSITY Alan Engelman OztopIlkerLentiviruses can infect postmitotic cells, indicative of a role for the nucleocytoplasmic transport machinery. Genome-wide RNA interference screens identified transportin 3 (TNPO3) that may regulate human immunodeficiency virus type 1 (...
CPSF6 is a 68 kDa member of the CPSF group that has been shown to target the HIV-1 viral capsid (CA) (6). A truncated form of CPSF6, CPSF6-358, localizes exclusively in the cytoplasm and can oligomerize to bind CA, restricting HIV infection and nuclear entry (7,8). ...
MxB’s effects on PIC nuclear import and HIV-1 replication depend critically on cofactor cleavage and polyadenylation specificity factor subunit 6 (CPSF6). MxB binds nucleoporin NUP358, blocks NUP358-CA interaction, thereby impeding the nuclear import of HIV-1 PIC with CPSF6 binding...
was therefore directed towards CPSF6, an SR-protein that binds HIV-1 CA and inhibits HIV-1 nuclear import when the C-terminal SR-domain is deleted. The effect of 27 HIV-1 capsid mutants on sensitivity to TNPO3 knockdown was then found to correlate strongly with sensitivity to inhibition by...
Human immunodeficiency virus type 1 (HIV-1) capsid binds to multiple host cell proteins after entry into a cell, including cyclophilin A (CypA) and cleavage and polyadenylation specificity factor 6 (CPSF6), which is expressed predominantly in the nucleus. As CPSF6 expression was observed in the...
Since miRNAs negatively regulate protein expression, we carried out knock-down and over-expression studies of miR-125b. Results from these experiments revealed that miR-125b expression is negatively associated with CPSF6 protein levels. Interestingly, HIV-1 infection resulted in the down-regulation ...
HIV-1 integration into the host genome favors actively transcribed genes. Prior work indicated that the nuclear periphery provides the architectural basis for integration site selection, with viral capsid-binding host cofactor CPSF6 and viral integrase-binding cofactor LEDGF/p75 contributing to selection ...
The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear e...
Upon HIV-1 infection, CPSF6 forms puncta in the nucleus. Here, we characterised these CPSF6 puncta further in HeLa cells, T-cells and macrophages and confirmed that integration and reverse transcription are not required for puncta formation. Indeed, we found that puncta formed very rapidly after...
liquid phase separation (LLPS) activity in vitro , the contributions of its different intrinsically disordered regions, which includes a central prion-like domain (PrLD) with capsid binding FG motif and C-terminal mixed-charge domain (MCD), to LLPS activity and to HIV-1 infection remain ...