Introduction: In addition, N74D and A105T render WT HIV-1 dependent on CypA-CA binding in H9 and HeLa cells, host cells that do not otherwise require CypA for WT HIV-1 replication.
Introduction: Interestingly, CA mutations N74D and A105T have no effect on the CA-CypA interaction, but, when encoded in cis, either mutant will rescue the infectivity defect of the A92E mutant.
HIV-1 evades innate immune recognition through specific cofactor recruitment.
Abstract: Here we show that HIV-1 capsid mutants N74D and P90A, which are impaired for interaction with cofactors cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), respectively, cannot replicate in primary human monocyte-derived macrophages because they trigger innate sensors leading to nuclear translocation of NF-kappaB and IRF3, the production of soluble type 1 IFN and induction of an antiviral state.
Introduction: Given that CA mutation N74D prevents recruitment of CPSF6 we hypothesized that CPSF6 depletion would induce WT HIV-1 to trigger IFN responses in MDM.
Introduction: HIV-1 capsid (CA) mutant N74D cannot recruit CPSF6 and is insens
The V86M mutation in HIV-1 capsid confers resistance to TRIM5alpha by abrogation of cyclophilin A-dependent restriction and enhancement of viral nuclear import.
Discussion: Indeed, restriction of HIV-1 by CPSF6-358, a truncated form of the RNA processing factor, cleavage and polyadenylation specific factor 6 (CPSF6), is counteracted by the mutation N74D in CA.
Differential effects of human immunodeficiency virus type 1 capsid and cellular factors nucleoporin 153 and LEDGF/p75 on the efficiency and specificity of viral DNA integration.
Abstract: Here, we show that CA mutations, which include the substitution of Asp for Asn74 (N74D), significantly reduce the dependency of HIV-1 on LEDGF/p75 during infection and that this difference correlates with the efficiency of viral DNA integration.
Abstract: The distribution of integration sites mapped by Illumina sequencing confirms that the N74D mutation reduces integration into gene-rich regions of chromosomes and gene bodies and reveals previously unrecognized roles for NUP153 (another HIV-1 cofactor implicated in viral nuclear import) and LEDGF/p75 in the targeting of the viral preintegration complex to gene-dense regions of chromatin.
Human immunodeficiency virus type 1 capsid mutation N74D alters cyclophilin A dependence and impairs macrophage infection.
Abstract: HIV-1 acquires resistance to CPSF6-358 through the N74D mutation of the capsid (CA), which alters its nuclear entry pathway.
Abstract: Here we show that compared to wild-type (WT) HIV-1, N74D HIV-1 is more sensitive to cyclosporine, has increased sensitivity to nevirapine, and is impaired in macrophage infection prior to reverse transcription.
Abstract: Overall, our data indicate that N74D HIV-1 replication in transformed cells requires cyclophilin A but is dependent on other interactions in macrophages.
Abstract: These phenotypes suggest a difference in the N74D reverse transcription complex that manifests early after infection and prior to interaction with the nuclear pore.
HIV-1 capsid-targeting domain of cleavage and polyadenylation specificity factor 6.
Result: Finally, we studied the HIV-1 CA mutant N74D, which is reported to be less sensitive to Nup358 or TRN-SR2 depletion (Figure 3A).
Result: For wild type HIV-1 this density was 15 transcription units/MB, whereas for CA mutants N57A or N74D the density was reduced to what is expected for random integration (7-9 transcription units/MB) (Figure 4A and Figure S7).
Result: HIV-1 CA
Result: Hierarchical clustering of the CA mutants based on these data separated the viruses into two groups: N57A and N74D, and the Cyp-binding mutants G89V, P90A and chimeric HIV-1(SIVCA) (Figure 4B).
Transportin 3 promotes a nuclear maturation step required for efficient HIV-1 integration.
Abstract: Depletion of Tnp3 results in a re-distribution of HIV-1 capsid proteins between nucleus and cytoplasm however HIV-1 bearing the N74D mutation in capsid, which is insensitive to Tnp3 depletion, does not show nucleocytoplasmic redistribution of capsid proteins.
Figure: (C) Control (Scr) and Tnp3 KD HeLa cells were infected with the N74D mutant vector and analyzed by flow cytometry 24 hours later; mean values +- SD of three independent experiments are shown.
Figure: Virus input was normalized for infectivity in HeLa cells, hence the higher amount of N74D CA detected at the 6h time point.
Discussion: Among the CA mutants tested, the N74D
The requirement for nucleoporin NUP153 during human immunodeficiency virus type 1 infection is determined by the viral capsid.
Abstract: Two capsid missense mutant viruses, N74D and P90A, were largely insensitive to NUP153 depletion, as was wild-type HIV-1 when cyclophilin A was depleted simultaneously or when infection was conducted in the presence of cyclosporine A.
HIV mutation literature information.
PMID: 
2014
Retrovirology
Browser Board
Co-occurred Entities
Filtrator
ViMRT