FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3199614052> ?p ?o ?g. }

• W3199614052 endingPage "e1009484" @default.
• W3199614052 startingPage "e1009484" @default.
• W3199614052 abstract "The capsid (CA) lattice of the HIV-1 core plays a key role during infection. From the moment the core is released into the cytoplasm, it interacts with a range of cellular factors that, ultimately, direct the pre-integration complex to the integration site. For integration to occur, the CA lattice must disassemble. Early uncoating or a failure to do so has detrimental effects on virus infectivity, indicating that an optimal stability of the viral core is crucial for infection. Here, we introduced cysteine residues into HIV-1 CA in order to induce disulphide bond formation and engineer hyper-stable mutants that are slower or unable to uncoat, and then followed their replication. From a panel of mutants, we identified three with increased capsid stability in cells and found that, whilst the M68C/E212C mutant had a 5-fold reduction in reverse transcription, two mutants, A14C/E45C and E180C, were able to reverse transcribe to approximately WT levels in cycling cells. Moreover, these mutants only had a 5-fold reduction in 2-LTR circle production, suggesting that not only could reverse transcription complete in hyper-stable cores, but that the nascent viral cDNA could enter the nuclear compartment. Furthermore, we observed A14C/E45C mutant capsid in nuclear and chromatin-associated fractions implying that the hyper-stable cores themselves entered the nucleus. Immunofluorescence studies revealed that although the A14C/E45C mutant capsid reached the nuclear pore with the same kinetics as wild type capsid, it was then retained at the pore in association with Nup153. Crucially, infection with the hyper-stable mutants did not promote CPSF6 re-localisation to nuclear speckles, despite the mutant capsids being competent for CPSF6 binding. These observations suggest that hyper-stable cores are not able to uncoat, or remodel, enough to pass through or dissociate from the nuclear pore and integrate successfully. This, is turn, highlights the importance of capsid lattice flexibility for nuclear entry. In conclusion, we hypothesise that during a productive infection, a capsid remodelling step takes place at the nuclear pore that releases the core complex from Nup153, and relays it to CPSF6, which then localises it to chromatin ready for integration." @default.
• W3199614052 created "2021-09-27" @default.
• W3199614052 creator A5023254532 @default.
• W3199614052 creator A5029253747 @default.
• W3199614052 creator A5031690071 @default.
• W3199614052 creator A5044354502 @default.
• W3199614052 creator A5050574367 @default.
• W3199614052 creator A5074499033 @default.
• W3199614052 date "2021-09-20" @default.
• W3199614052 modified "2023-10-18" @default.
• W3199614052 title "HIV-1 requires capsid remodelling at the nuclear pore for nuclear entry and integration" @default.
• W3199614052 cites W1517131856 @default.
• W3199614052 cites W1572583106 @default.
• W3199614052 cites W1770932653 @default.
• W3199614052 cites W1925325850 @default.
• W3199614052 cites W1964022123 @default.
• W3199614052 cites W1972583115 @default.
• W3199614052 cites W1975534778 @default.
• W3199614052 cites W1976118295 @default.
• W3199614052 cites W1981574379 @default.
• W3199614052 cites W1985700039 @default.
• W3199614052 cites W2000218608 @default.
• W3199614052 cites W2003527687 @default.
• W3199614052 cites W2006105386 @default.
• W3199614052 cites W2006519535 @default.
• W3199614052 cites W2007040549 @default.
• W3199614052 cites W2018400595 @default.
• W3199614052 cites W2020597127 @default.
• W3199614052 cites W2021064626 @default.
• W3199614052 cites W2023247488 @default.
• W3199614052 cites W2025244778 @default.
• W3199614052 cites W2038356077 @default.
• W3199614052 cites W2054099226 @default.
• W3199614052 cites W2060904385 @default.
• W3199614052 cites W2061714407 @default.
• W3199614052 cites W2066409312 @default.
• W3199614052 cites W2073273867 @default.
• W3199614052 cites W2076965602 @default.
• W3199614052 cites W2077915242 @default.
• W3199614052 cites W2078109757 @default.
• W3199614052 cites W2082314789 @default.
• W3199614052 cites W2082325642 @default.
• W3199614052 cites W2084938297 @default.
• W3199614052 cites W2098641580 @default.
• W3199614052 cites W2107066237 @default.
• W3199614052 cites W2109870705 @default.
• W3199614052 cites W2111673257 @default.
• W3199614052 cites W2115851369 @default.
• W3199614052 cites W2116743728 @default.
• W3199614052 cites W2117091532 @default.
• W3199614052 cites W2120792521 @default.
• W3199614052 cites W2121043600 @default.
• W3199614052 cites W2121753315 @default.
• W3199614052 cites W2122523609 @default.
• W3199614052 cites W2135035609 @default.
• W3199614052 cites W2139119391 @default.
• W3199614052 cites W2145848202 @default.
• W3199614052 cites W2156696460 @default.
• W3199614052 cites W2161243122 @default.
• W3199614052 cites W2165070219 @default.
• W3199614052 cites W2167913336 @default.
• W3199614052 cites W2170915201 @default.
• W3199614052 cites W2172125721 @default.
• W3199614052 cites W2176753208 @default.
• W3199614052 cites W2299744993 @default.
• W3199614052 cites W2308758579 @default.
• W3199614052 cites W2469377523 @default.
• W3199614052 cites W2470514477 @default.
• W3199614052 cites W2513660300 @default.
• W3199614052 cites W2565695020 @default.
• W3199614052 cites W2744923425 @default.
• W3199614052 cites W2748845569 @default.
• W3199614052 cites W2796781674 @default.
• W3199614052 cites W2807506288 @default.
• W3199614052 cites W2807878793 @default.
• W3199614052 cites W2886118395 @default.
• W3199614052 cites W2913454226 @default.
• W3199614052 cites W2979340291 @default.
• W3199614052 cites W2986034299 @default.
• W3199614052 cites W2999273731 @default.
• W3199614052 cites W3007556991 @default.
• W3199614052 cites W3014660159 @default.
• W3199614052 cites W3031494023 @default.
• W3199614052 cites W3040374393 @default.
• W3199614052 cites W3042510281 @default.
• W3199614052 cites W3090229697 @default.
• W3199614052 cites W3092270865 @default.
• W3199614052 cites W3093404578 @default.
• W3199614052 cites W3095277531 @default.
• W3199614052 cites W3106634380 @default.
• W3199614052 cites W3186179214 @default.
• W3199614052 cites W339849909 @default.
• W3199614052 doi "https://doi.org/10.1371/journal.ppat.1009484" @default.
• W3199614052 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8483370" @default.
• W3199614052 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34543344" @default.
• W3199614052 hasPublicationYear "2021" @default.
• W3199614052 type Work @default.
• W3199614052 sameAs 3199614052 @default.

• next