Publications by authors named "Anselmo Jiro Kamada"

9 Publications

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Virus-derived variation in diverse human genomes.

PLoS Genet 2021 Apr 26;17(4):e1009324. Epub 2021 Apr 26.

Genome Immunobiology RIKEN Hakubi Research Team, RIKEN Center for Integrative Medical Sciences and RIKEN Cluster for Pioneering Research, Yokohama, Japan.

Acquisition of genetic material from viruses by their hosts can generate inter-host structural genome variation. We developed computational tools enabling us to study virus-derived structural variants (SVs) in population-scale whole genome sequencing (WGS) datasets and applied them to 3,332 humans. Although SVs had already been cataloged in these subjects, we found previously-overlooked virus-derived SVs. We detected non-germline SVs derived from squirrel monkey retrovirus (SMRV), human immunodeficiency virus 1 (HIV-1), and human T lymphotropic virus (HTLV-1); these variants are attributable to infection of the sequenced lymphoblastoid cell lines (LCLs) or their progenitor cells and may impact gene expression results and the biosafety of experiments using these cells. In addition, we detected new heritable SVs derived from human herpesvirus 6 (HHV-6) and human endogenous retrovirus-K (HERV-K). We report the first solo-direct repeat (DR) HHV-6 likely to reflect DR rearrangement of a known full-length endogenous HHV-6. We used linkage disequilibrium between single nucleotide variants (SNVs) and variants in reads that align to HERV-K, which often cannot be mapped uniquely using conventional short-read sequencing analysis methods, to locate previously-unknown polymorphic HERV-K loci. Some of these loci are tightly linked to trait-associated SNVs, some are in complex genome regions inaccessible by prior methods, and some contain novel HERV-K haplotypes likely derived from gene conversion from an unknown source or introgression. These tools and results broaden our perspective on the coevolution between viruses and humans, including ongoing virus-to-human gene transfer contributing to genetic variation between humans.
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http://dx.doi.org/10.1371/journal.pgen.1009324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101998PMC
April 2021

Endogenization and excision of human herpesvirus 6 in human genomes.

PLoS Genet 2020 08 10;16(8):e1008915. Epub 2020 Aug 10.

Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.

Sequences homologous to human herpesvirus 6 (HHV-6) are integrated within the nuclear genome of about 1% of humans, but it is not clear how this came about. It is also uncertain whether integrated HHV-6 can reactivate into an infectious virus. HHV-6 integrates into telomeres, and this has recently been associated with polymorphisms affecting MOV10L1. MOV10L1 is located on the subtelomere of chromosome 22q (chr22q) and is required to make PIWI-interacting RNAs (piRNAs). As piRNAs block germline integration of transposons, piRNA-mediated repression of HHV-6 integration has been proposed to explain this association. In vitro, recombination of the HHV-6 genome along its terminal direct repeats (DRs) leads to excision from the telomere and viral reactivation, but the expected "solo-DR scar" has not been described in vivo. Here we screened for integrated HHV-6 in 7,485 Japanese subjects using whole-genome sequencing (WGS). Integrated HHV-6 was associated with polymorphisms on chr22q. However, in contrast to prior work, we find that the reported MOV10L1 polymorphism is physically linked to an ancient endogenous HHV-6A variant integrated into the telomere of chr22q in East Asians. Unexpectedly, an HHV-6B variant has also endogenized in chr22q; two endogenous HHV-6 variants at this locus thus account for 72% of all integrated HHV-6 in Japan. We also report human genomes carrying only one portion of the HHV-6B genome, a solo-DR, supporting in vivo excision and possible viral reactivation. Together these results explain the recently-reported association between integrated HHV-6 and MOV10L1/piRNAs, suggest potential exaptation of HHV-6 in its coevolution with human chr22q, and clarify the evolution and risk of reactivation of the only intact (non-retro)viral genome known to be present in human germlines.
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http://dx.doi.org/10.1371/journal.pgen.1008915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7444522PMC
August 2020

Perforin gene PRF1 c.900C> T polymorphism and HIV-1 vertical transmission.

Genet Mol Biol 2019 Jul-Sep;42(3):574-577. Epub 2019 Nov 14.

Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

Perforin-1, a component of the immune system, is able to control Human Immunodeficiency Virus-1 (HIV-1) replication and could be involved in HIV-1 mother-to-child transmission (MTCT). This study aims at evaluating the role of the c.900C > T PRF1 gene (encoding for perforin-1) polymorphism (rs885822) in HIV-1 MTCT. The PRF1 c.900C > T polymorphism was genotyped in 331 children from Zambia using a Taqman probe on a Real Time PCR platform. The PRF1 c.900C > T C/T genotype was more frequent among HIV-1 exposed but non-infected children than in HIV-1 positive cases, and the results were confirmed among children infected during breastfeeding. PRF1 c.900C > T correlated with protection against HIV-1 MTCT, suggesting its role in HIV-1 vertical transmission.
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http://dx.doi.org/10.1590/1678-4685-GMB-2018-0243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905447PMC
November 2019

polymorphisms and HIV-1 mother-to-child transmission in Zambian population.

J Matern Fetal Neonatal Med 2019 Sep 20;32(17):2805-2811. Epub 2018 Mar 20.

b Institute for Maternal and Child Health - IRCCS "Burlo Garofolo" , Trieste , Italy.

Human Beta Defensin-1 (hBD-1) is a component of the innate immune system, the first line of defence against pathogens, already reported as involved in the susceptibility to HIV-1 infection and HIV-1 mother-to-child transmission (MTCT) in different populations. We investigated the role of gene (encoding for hBD-1) functional polymorphisms in the susceptibility to HIV-1 MTCT in a population from Zambia. Four selected polymorphisms within gene, three at the 5' untranslated region (UTR), namely -52G > A (rs1799946), -44C > G (rs1800972) and -20G > A (rs11362) and one in the 3'UTR, c.*87A > G (rs1800972), were genotyped in 101 HIV-1 positive mothers (26 transmitters -27% and 75 not transmitters -73%) and 331 infants born to HIV-1 infected mothers (85 HIV-1 positive -26% and 246 exposed but not infected -74%). c.*87-A allele was more frequent among HIV- children with respect to HIV+ (with intrauterine MTCT). Concerning haplotypes, GCGA haplotype resulted more represented in HIV- than HIV+ infants and ACGG haplotype presented increased frequency in HIV- children respect to HIV+ (with intra-partum MTCT) ( = .02,  = .002 and  = .006, respectively). polymorphisms were significantly associated with decreased risk of HIV-1 infection acquisition in the studied Zambian population suggesting that they may play a role in HIV-1 MTCT.
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http://dx.doi.org/10.1080/14767058.2018.1449206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202264PMC
September 2019

Association Between LTF Polymorphism and Risk of HIV-1 Transmission Among Zambian Seropositive Mothers.

Curr HIV Res 2018 ;16(1):52-57

Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, Italy.

Background: Lactoferrin is a member of the innate immune system acting in the first line of defence against pathogens, and it is known for its antibacterial, antifungal and antiviral activity, including HIV-1. Two polymorphisms, T29A and R47K, in the exon 1 region of the LTF gene (encoding for the lactoferrin protein) were previously described as able to influence the lactoferrin antimicrobial function.

Objectives: LTF T29A and R47K genetic variants were analysed in a Zambian population to unravel if these polymorphisms could play a role in HIV-1 mother-to-child HIV-1 transmission.

Methods: LTF T29A and R47K polymorphisms were genotyped, using allelic specific fluorescent probes and real time PCR, in a population comprising 101 HIV-1 positive mothers and 333 children born to seropositive mothers.

Results: Maternal LTF T29A A/A and A/G genotypes were found to be associated with decreased risk of HIV-1 MTCT, being more frequent among non-transmitter mothers respect to transmitter mothers.

Conclusion: Our data suggested that maternal LTF genetic background contributes to the susceptibility to HIV-1 transmission from mother to new-borns.
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http://dx.doi.org/10.2174/1570162X15666171120105752DOI Listing
April 2019

Association of HLA-G 3'UTR polymorphisms and haplotypes with severe sepsis in a Brazilian population.

Hum Immunol 2017 Nov 21;78(11-12):718-723. Epub 2017 Sep 21.

Department of Genetics, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil. Electronic address:

Background: The human leukocyte antigen G (HLA-G) is a molecule involved in immune system modulation, acting in the maintenance of a state of immune tolerance. Some polymorphisms in the HLA-G gene 3' untranslated region (3'UTR) were associated to distinct levels of HLA-G expression and to sepsis development. In the present study, haplotypes and polymorphisms of the HLA-G 3'UTR were analyzed in Brazilian septic patients.

Methods: The HLA-G 3'UTR was amplified by PCR, sequenced and eight polymorphisms were genotyped (the 14bp insertion/deletion, +3003T/C, +3010C/G, +3027A/C, +3035C/T, +3142G/C, +3187A/G and+3196C/G) in DNA samples from septic patients (with severe sepsis or septic shock) and controls. The haplotypes were inferred and association tests were performed through Chi square test and binary logistic regression.

Results: The+3027AC genotype was associated asa risk factor to sepsis development (OR 3.17, P 0.048). Further, the presence of the UTR-7 haplotype (OR 2.97, P 0.018), and of 14bp-Ins_+3142G_+3187A haplotype (OR 2.39, P 0.045) were associated with sepsis, conferring susceptibility.

Conclusion: Our data confirm an important role of HLA-G 3'UTR polymorphisms in the development of severe forms of sepsis (severe sepsis and septic shock). The genotyping of HLA-G genetic variants and haplotypes could be useful as a prediction tool of increased risk to severe sepsis.
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http://dx.doi.org/10.1016/j.humimm.2017.09.002DOI Listing
November 2017

Dendritic Cell-Based Immunotherapies to Fight HIV: How Far from a Success Story? A Systematic Review and Meta-Analysis.

Int J Mol Sci 2016 Nov 26;17(12). Epub 2016 Nov 26.

IRCCS Burlo Garofolo and University of Trieste, Via dell' Istria 65/1, Trieste 34137, Italy.

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%-51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.
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http://dx.doi.org/10.3390/ijms17121985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187785PMC
November 2016

Meta-analysis and time series modeling allow a systematic review of primary HIV-1 drug-resistant prevalence in Latin America and Caribbean.

Curr HIV Res 2015 ;13(2):125-42

Department of Genetics, Universidade Federal de Pernambuco, Avenida da Engenharia, Cidade Universitaria, Recife, PE, Postal Code: 50740-600, Brazil.

Here we review the prevalence of HIV-1 primary drug resistance in Latin America and Caribbean using meta-analysis as well as time-series modeling. We also discuss whether there could be a drawback to HIV/AIDS programs due to drug resistance in Latin America and Caribbean in the next years. We observed that, although some studies report low or moderate primary drug resistance prevalence in Caribbean countries, this evidence needs to be updated. In other countries, such as Brazil and Argentina, the prevalence of drug resistance appears to be rising. Mutations conferring resistance against reverse transcriptase inhibitors were the most frequent in the analyzed populations (70% of all mutational events). HIV-1 subtype B was the most prevalent in Latin America and the Caribbean, although subtype C and B/F recombinants have significant contributions in Argentina and Brazil. Thus, we suggest that primary drug resistance in Latin America and the Caribbean could have been underestimated. Clinical monitoring should be improved to offer better therapy, reducing the risk for HIV-1 resistance emergence and spread, principally in vulnerable populations, such as men who have sex with men transmission group, sex workers and intravenous drug users.
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http://dx.doi.org/10.2174/1570162x13999150317155040DOI Listing
January 2016

NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection.

Mem Inst Oswaldo Cruz 2014 Nov;109(7):960-3

Departamento de Patologia, Universidade Federal de Pernambuco, Recife, PE, Brasil.

Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1) infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL)-1 family (IL-1, IL-18 and IL-33) members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls). NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37). rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.
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November 2014
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