Role of APOBEC3F Gene Variation in HIV-1 Disease Progression and Pneumocystis Pneumonia

An, Ping; Penugonda, Sudhir; Thorball, Christian W.; Bartha, István; Goedert, James J.; Donfield, Sharyne; Buchbinder, Susan; Binns-Roemer, Elizabeth; Kirk, Gregory D.; Zhang, Wenyan; Fellay, Jacques; Yu, Xiao Fang; Winkler, Cheryl A.

doi:10.1371/journal.pgen.1005921

Cited by 19 publications

(19 citation statements)

References 74 publications

(100 reference statements)

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“…Полиморфизм rs2076101G (231V) гена APOBEC3F значимо коррелирует с пониженным уровнем равновесной вирусной нагрузки и замедлением развития СПИДа. Протективный ýффект гаплотипа 231V особенно выражен у ВИЧ-инфицированных пациентов, страдающих пневмоцистной пневмонией, -развитие оппортунистической инфекции замедляется [19]. Существует значительная вариабельность в индивидуальной чувствительности к ВИЧ-инфекции и в клинической картине заболевания.…”

Section: гены Apobec3unclassified

Allelic variants of human genes affecting HIV intracellular life cycle and regulating immune response to HIV infection

et al. 2019

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Host genetic factors influencing the intracellular part of HIV live cycle and regulating of HIV-specific immune response are reviewed. Its include genes coding proteins which support viral replication and assembly of new virions, genes coding antiviral defense proteins, HLA genes and some others. Variants of these genes and its compositions affect individual succeptibility/resistance to HIV infection, influence the pathogenesis of the disease and also associate with efficacy of antiretroviral therapy.

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Section: гены Apobec3unclassified

Allelic variants of human genes affecting HIV intracellular life cycle and regulating immune response to HIV infection

et al. 2019

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“…The apolipoprotein mRNA editing enzyme catalytic polypeptide-like 3 (APOBEC3; A3) proteins are a family of seven cytidine deaminases (A3A, A3B, A3C, A3D, A3F, A3G, and A3H) that restrict certain lentiviruses, retrotransposons, hepatitis B virus and human papillomavirus [1][2][3][4]. Many studies focused on the genes A3F, A3G, and A3H because of their innate defense ability to restrict the replication of the HIV-1 [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

“…Particularly, A3G mutates primarily TGGs when this codon is followed by a G (TGGG). On the other hand, A3F, A3D, and A3H mutate TGG into the TGA stop codon when the TGG codon is followed by an A (TGGA) [1,2,8]. a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 HIV-1 counteracts the antiviral property of A3 proteins by the activity of the viral [16,21,[23][24][25] infectivity factor (Vif).…”

Section: Introductionmentioning

confidence: 99%

Is the tryptophan codon of gene vif the Achilles’ heel of HIV-1?

2020

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To evaluate the impact of hypermutation on the HIV-1 dissemination at the population level we studied 7072 sequences HIV-1 gene vif retrieved from the public databank. From this dataset 854 sequences were selected because they had associated values of CD4+ T lymphocytes counts and viral loads and they were used to assess the correlation between clinical parameters and hypermutation. We found that the frequency of stop codons at sites 5, 11 and 79 ranged from 2.8x10-4 to 4.2x10-4. On the other hand, at codons 21, 38, 70, 89 and 174 the frequency of stop codons ranged from 1.4x10-3 to 2.5x10-3. We also found a correlation between clinical parameters and hypermutation where patients harboring proviruses with one or more stop codons at the tryptophan sites of the gene vif had higher CD4+ T lymphocytes counts and lower viral loads compared to the population. Our findings indicate that A3 activity potentially restrains HIV-1 replication because individuals with hypermutated proviruses tend to have lower numbers of RNA copies. However, owing to the low frequency of hypermutated sequences observed in the databank (44 out of 7072), it is unlikely that A3 has a significant impact to curb HIV-1 dissemination at the population level.

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“…Three other members of the APOBEC family, APOBEC3D (A3D), APOBEC3F (A3F), and APOBEC3H (A3H) can also be packaged into HIV particles and inhibit viral replication, when stably expressed in human T-cell lines [5]. Endogenous A3D and A3F combine to generate the 5′-GA-to-AA mutation pattern observed in vif -negative HIV grown in the non-permissive T-cell line CEM2n [6, 7]. Of the seven different human haplotypes of APOBEC3H, only hapII, hapV and hapVII are stable at the protein level and capable of HIV restriction [8–12].…”

Section: Introductionmentioning

confidence: 99%

Characterization of APOBEC3 variation in a population of HIV-1 infected individuals in northern South Africa

et al. 2019

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BackgroundThe apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3 (APOBEC3) genes A3D, A3F, A3G and A3H have all been implicated in the restriction of human immunodeficiency virus type 1 (HIV-1) replication. Polymorphisms in these genes are likely to impact viral replication and fitness, contributing to viral diversity. Currently, only a few studies indicate that polymorphisms in the A3 genes may be correlated with infection risk and disease progression.MethodsTo characterize polymorphisms in the coding regions of these APOBEC3 genes in an HIV-1 infected population from the Limpopo Province of South Africa, APOBEC3 gene fragments were amplified from genomic DNA of 192 HIV-1 infected subjects and sequenced on an Illumina MiSeq platform. SNPs were confirmed and compared to SNPs in other populations reported in the 1000 Genome Phase III and HapMap databases, as well as in the ExAC exome database. Hardy-Weinberg Equilibrium was calculated and haplotypes were inferred using the LDlink 3.0 web tool. Linkage Disequilibrium (LD) for these SNPS were calculated in the total 1000 genome and AFR populations using the same tool.ResultsKnown variants compared to the GRCh37 consensus genome sequence were detected at relatively high frequencies (> 5%) in all of the APOBEC3 genes. A3H showed the most variation, with several of the variants present in both alleles in almost all of the patients. Several minor allele variants (< 5%) were also detected in A3D, A3F and A3G. In addition, novel R6K, L221R and T238I variants in A3D and I117I in A3F were observed. Four, five, four, and three haplotypes were identified for A3D, A3F, A3G, and A3H respectively.ConclusionsThe study showed significant polymorphisms in the APOBEC3D, 3F, 3G and 3H genes in our South African HIV1-infected cohort. In the case of all of these genes, the polymorphisms were generally present at higher frequencies than reported in other 1000 genome populations and in the ExAC exome consortium database .Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0740-4) contains supplementary material, which is available to authorized users.

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Role of APOBEC3F Gene Variation in HIV-1 Disease Progression and Pneumocystis Pneumonia

Cited by 19 publications

References 74 publications

Allelic variants of human genes affecting HIV intracellular life cycle and regulating immune response to HIV infection

Allelic variants of human genes affecting HIV intracellular life cycle and regulating immune response to HIV infection

Is the tryptophan codon of gene vif the Achilles’ heel of HIV-1?

Characterization of APOBEC3 variation in a population of HIV-1 infected individuals in northern South Africa

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