Publications by authors named "V Kewalramani"
HIV-1 integration favors nuclear speckle (NS)-proximal chromatin and viral infection induces the formation of capsid-dependent CPSF6 condensates that colocalize with nuclear speckles (NSs). Although CPSF6 displays liquid-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 unclear. Herein, we determined that the PrLD and MCD both contribute to CPSF6 LLPS activity in vitro.
View Article and Find Full Text PDFThe early events of HIV-1 infection involve the transport of the viral core into the nucleus. This event triggers the translocation of CPSF6 from paraspeckles into nuclear speckles forming puncta-like structures. Our investigations revealed that neither HIV-1 integration nor reverse transcription is required for the formation of puncta-like structures.
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- Scientists are trying to understand how viruses, like HIV-1, get into the cell's nucleus through special openings called nuclear pore complexes (NPCs).
- They found that a part of the HIV-1 virus called the capsid (CA) is really important for this process, as it interacts with specific proteins called nucleoporins (Nups) in the NPCs.
- Researchers discovered that certain nucleoporins (Nup35, Nup153, and POM121) help HIV-1 get inside the nucleus, and that if the capsid is changed or certain host factors are removed, the virus has a harder time getting in.
Article Synopsis
- Cellular proteins CPSF6, NUP153, and SEC24C are critical for HIV-1 infection, but how they interact with mature HIV-1 capsid structures is not well understood.
- The study demonstrates that low complexity regions (LCRs) of CPSF6 facilitate strong binding to HIV-1 capsid lattices through specific interactions with hydrophobic pockets on the capsid.
- Additionally, the drug lenacapavir targets these hydrophobic pockets, impairing HIV-1's functionality in the nucleus without displacing the cellular proteins, revealing new mechanisms for virus-host interactions and potential antiviral strategies.
Retroviruses utilize the viral integrase (IN) protein to integrate a DNA copy of their genome into host chromosomal DNA. HIV-1 integration sites are highly biased towards actively transcribed genes, likely mediated by binding of the IN protein to specific host factors, particularly LEDGF, located at these gene regions. We here report a substantial redirection of integration site distribution induced by a single point mutation in HIV-1 IN.
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