Discussion: In addition, depletion of TRIM5alphahu expression in CD4+ T cells rescued infectivity of HIV-1-P90A viruses.
Discussion: Mutant HIV-1 (P90A or G89V) infection of PBMCs or CD4+ T cells was 10-20-fold weaker than that of wild-type HIV-1.
Discussion: Mutations in the CypA-binding loop of the capsid, such as P90A and G89V, cause an infectivity defect similar to that caused by CsA treatment during wild-type HIV-1 infection of Jurkat and CD4+ T cells; however, infection of HIV-1 viruses bearing the capsid change A92E or G94D results in an infection that is insensitive to CsA treatment in Jurkat cells.
TRIM34 restricts HIV-1 and SIV capsids in a TRIM5alpha-dependent manner.
Introduction: Further, both the HIV-1 P90A capsid mutant and the HIV-1 N74D capsid mutant, referred to hereafter as P90A and N74D respectively, have been shown to be hypersensitive to the effects of IFN, suggesting that one or more IFN-induced restriction factors block infection of these capsid mutant viruses.
Introduction: Further, we find that TRIM34 requires TRIM5alpha to inhibit N74D while inhibition of P90A occurs independent of TRIM34.
Introduction: Here we use this approach to identify capsid-targeting restrictions that target the P90A and N74D HIV-1 capsid mutants.
MxB sensitivity of HIV-1 is determined by a highly variable and dynamic capsid surface.
Result: In a control experiment, HIV-1 CA P90A was treated with CsA during infection of MxB expressing cells and we observed no rescue to infectivity, consistent with P90A being resistant to MxB due to failure to recruit CypA (Figure 3F).
Figure: (f) HIV-1 GFP WT (left) or P90A (right) vector titre on HEK293 cells untreated (UT) or treated with Dox to induce MxB expression (+Dox (MxB)) and depleted of TNPO3 by shRNA transduction.
Figure: (i) HIV-1 GFP WT (left) or P90A (right) vector titre on HEK293 cells untreated (UT) or treated with Dox to induce MxB expression (+Dox (MxB)) and depleted of Nup358 by shRNA transduction.
Discussion: Indeed, we observe that, despite insensitivity to MxB mediated inhibition of infectivity, proviral DNA levels of HIV-1 bearing CA
A non-canonical role for the autophagy machinery in anti-retroviral signaling mediated by TRIM5alpha.
Abstract: Moreover, we found that the ability of TRIM5alpha to stimulate IFN-beta expression in response to recognition of a TRIM5alpha-restricted HIV-1 capsid mutant (P90A) was abrogated in cells lacking autophagy factors.
Abstract: Stimulation of human macrophage-like cells with the P90A virus protected them against subsequent infection with an otherwise resistant wild type HIV-1 in a manner requiring TRIM5alpha, BECN1, and ULK1.
Method: Media containing VSV-G pseudotyped lentiviral vectors expressing HIV1 WT or HIV1-P90A or N-MLV was added to infect cells in a total volume of 100 muL in the presence of polybrene.
Method: THP1 control and the different THP1 KO cells were seeded into 96 well plates at a density of 50000 cells/well, differentiated with PMA, then primed with VSV-G pseudotyped HIV-mCherry (at a CrFK MOI of 3) or VSV-G ps
Multiple Pathways To Avoid Beta Interferon Sensitivity of HIV-1 by Mutations in Capsid.
Introduction: Specifically, it was reported that the CypA binding-deficient CA mutant (the P90A mutant) and the CPSF6 binding-deficient CA mutant (the N74D and A105T mutant) are more sensitive than wild-type (WT) CA to IFN alpha (IFN-alpha) in monocyte-derived THP-1 cells.
Result: In agreement with previous reports, the N74D and P90A viruses were more resistant to MxB than the WT virus.
Result: Previous studies demonstrated that the impaired infectivity of CsA-dependent CA mutants, including those with the A92E and G94D mutations, in certain cell types was rescued by additional PMID: 27279606
2016
Journal of virology
Abstract: As expected, CypA depletion had no additional effect on the behavior of the P90A mutant but modestly increased the IFN-alpha sensitivity of wild-type virus.
Abstract: Interestingly, the infectivity of wild-type or P90A virus could be rescued from the MX2-independent IFN-alpha-induced blocks in THP-1 cells by treatment with cyclosporine (Cs) or its nonimmunosuppressive analogue SDZ-NIM811, indicating that Cs-sensitive host cell cyclophilins other than CypA contribute to the activity of IFN-alpha-induced blocks.
Abstract: We show here that the HIV-1 CA mutations N74D and A105T, both of which allow escape from inhibition by MX2 and the truncated version of cleavage and polyadenylation specific factor 6 (CPSF6), as well as the cyclophilin A (CypA)-binding loop mutation P90A
KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection.
Figure: (A) MDM or HeLa cells were synchronously infected HIV-1 GFP pseudotyped with VSV-g bearing either the wildtype (WT) CA or N74D and P90A CA mutants(MDMs MOI 0.3, HeLa MOI 0.6).Cells fixed at 3h post infection, incubated with primary antibodies to Nup358 and HIV-1 CA, followed by secondary antibodies specific for these antibodies conjugated to the PLUS and MINUS PLA oligonucleotides.
Figure: (A,B) Monocyte derived macrophages (MDM) and HeLa cells were synchronously infected with VSVg pseudotyped HIV-1 reporter virus (MOI 0.3 for MDM and MOI 0.6 for HeLa cells) bearing either the wildtype (WT) CA or N74D and
An HIV-1 capsid binding protein TRIM11 accelerates viral uncoating.
Result: E45A mutant has been reported to increase the capsid stability, N74D resides in a conserved hydrophobic binding pocket, while P90A, G89V and G94V reside in the CypA-binding loop.
Result: In contrast, the effect of TRIM11 on HIV-1 reverse transcription was abolished by capsid mutation G89V, and compromised by capsid mutation P90A.
Cyclophilin A promotes HIV-1 reverse transcription but its effect on transduction correlates best with its effect on nuclear entry of viral cDNA.
Introduction: The relevance of the CA-CypA interaction for HIV-1 replication has been demonstrated using multiple experimental approaches, including disruption of binding with the competitive inhibitor cyclosporine A (CsA), CA mutants G89V and P90A, CypA mutants in the active site, and depletion of endogenous CypA by gene knock-out or RNA knock-down.
Method: p8.9NdSB bearing G89V, G89V/A92E, P90A, P90A/A92E, A92E, A92E/A105T and A105T in the CA sequence were previ
A cyclophilin homology domain-independent role for Nup358 in HIV-1 infection.
Result: We challenged cells over a range of viral inputs with this virus, HIV-1, HIV-1 cyclophilin binding mutant capsid viruses (P90A, G89A<
Discussion: Fourth, we analyzed the phenotypes of HIV-1 capsid mutants, including the TNPO3 interaction-defective N74D, and cyclophilin binding mutants P90A, G89A, and G89V.
Discussion: In HeLa cells and monocyte-derived macrophages (MDM), differential effects between wild type HIV-1 and such viruses led to the proposal that a sequential CypA-Nup358 CHD interaction regulates core uncoating and that the failure of P90A HIV-1 to propagate in MDM (and the block imposed in these cells by CsA) may be due to inability to access this pathway.
HIV mutation literature information.
PMID: 
2020
Cell reports
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