Abstract: In selection experiments with subtype C HIV-1, we identified mutations at CA residue 230 (CA-V230M) and SP1 residue 1 (SP1-A1V), residue 5 (SP1-S5N), and residue 10 (SP1-G10R).
Insight into the mechanism of action of EP-39, a bevirimat derivative that inhibits HIV-1 maturation.
Abstract: Finally, using NMR, we have shown that the interaction of EP-39 with a peptide carrying the SP1-A1V mutation (CA-SP1(A1V)-NC) is almost suppressed in comparison with the wild type peptide.
Abstract: W
Abstract: We also identified six mutations that confer BVM resistance (CA-A194T, CA-L231F, CA-L231M, SP1-A1V, SP1-S5N and SP1-V7A).
Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly.
Abstract: Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site.
Result: Furthermore, the A1V/S40F mutant displayed a similar CA processing compared to the wt.
Figure: (C) Specific infectivity of HIV-1NL4-3 wt and S40F mutant in combination with the A1V mutation.
Discussion: Interestingly, the effect of the S40F mutation appears to be specific for the CA-SP1 cleavage inas
Polymorphisms in Gag spacer peptide 1 confer varying levels of resistance to the HIV- 1 maturation inhibitor bevirimat.
Conclusion: The SP1-V7A mutant displayed full resistance to BVM in terms of CA-SP1 processing, single-cycle infectivity, and virus replication assays, and its resistance was comparable to that of the robust and frequently observed BVM-resistance mutant SP1-A1V.
Result: Replication of SP1-T8Delta was significantly delayed at the 50 ng/ml BVM concentration and was only detected upon acquisition of the SP1-
Result: WT pNL4-3, which contains the QVT motif at SP1/6-8, was used as a BVM-susceptible virus and the previously characterized SP1-A1V mutant served as a prototypical BVM-resistant virus.
[Prediction of the efficacy of bevirimat used for the treatment of HIV infection in Russia].
Abstract: The nucleotide sequences coding the CA-SP1 Pr55(gag) in 61 samples of HIV-1 subtype A variant IDU-A isolated in Russia were analyzed for bevirimat resistance mutations (CA-H226V, CA-L231F, CA-231M, SP1-A1V, SP1-A3T, SP1-A3V) and for polymorphisms in the GAG CA-SP1 cleavage site.
Impact of human immunodeficiency virus type 1 resistance to protease inhibitors on evolution of resistance to the maturation inhibitor bevirimat (PA-457).
Abstract: Significantly, the emergence of BVM resistance was delayed in the context of the PIR PR, and the SP1-A1V mutation was acquired most frequently with either WT or PIR PR.
Abstract: The BVM-resistant mutant SP1-A1V was an exception, as it supported robust replication in the context of either wild-type (WT) or PIR PR, even at high BVM concentrations.
Abstract: We predict that the SP1-A1V substitution is the most likely to emerge in vivo, as this mutant replicates robustly independently of PR mutations or BVM.
Primary genotypic resistance of HIV-1 to the maturation inhibitor PA-457 in protease inhibitor-experienced patients.
Abstract: Sequences from 82 protease inhibitors (PI)-experienced patients were analysed for the presence of previously described in-vitro resistance mutations to PA-457 located in the C-terminal capside (H226Y, L231F, L231M) and in the N-terminal SP1 (A1V, A3T, A3V) within the CA-SP1 boundary domain.
Potent activity of the HIV-1 maturation inhibitor bevirimat in SCID-hu Thy/Liv mice.
Method: Stocks of NL4-3 and SP1/A1V were prepared by transfection of 293T cells and collection of supernatants on days 2 or 3.
Resul
Figure: Bevirimat-resistant SP1/A1V replicates and depletes thymocytes with kinetics comparable to wild-type NL4-3 in SCID-hu Thy/Liv mice.
Figure: In Vivo Competitions Reveal No Impairment of SP1/A1V Replication.
Figure: Sequencing of CA-SP1 RNA from three SCID-hu Thy/Liv mice coinfected with equivalent infectious units of NL4-3 and SP1/A1V reveal no impairment of SP1/A1V replication 28 days after implant inoculation.
3-O-(3',3'-dimethysuccinyl) betulinic acid inhibits maturation of the human immunodeficiency virus type 1 Gag precursor assembled in vitro.
HIV mutation literature information.
PMID: 
2021
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