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.
Figure: C, HIV-1 capsid mutants that are less sensitive to Nup358, Nup153 or TRN-SR2 RNAi (HIV-1 CA N57A or N74D) enter the nucleus through a different pathway that directs their integration into genome areas of lower density of transcription units.
Figure: D, Depletion of Nup358 by RNAi reduces viral nuclear entry via the Nup358-dependent pathway and the virus gains access via an Nup358-independent alternative pathway resulting in phenotypically similar integration site selection as observed for the
Discussion: Furthermore, mutations that render HIV-1 less sensitive to both Nup358 and TRN-SR2 depletion (CA N57A and N74D) both shift integration preferences to regions with lower densities of transcription units (Figure 4).
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.
Result: A different intracellular distribution of wild type and N74D 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.
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