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1.
Retrovirology ; 13: 6, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26767784

RESUMO

BACKGROUND: Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that have invaded the germ line of both humans and non-human primates. Most ERVs are functionally crippled by deletions, mutations, and hypermethylation, leading to the view that they are inert genomic fossils. However, some ERVs can produce mRNA transcripts, functional viral proteins, and even non-infectious virus particles during certain developmental and pathological processes. While there have been reports of ERV-specific immunity associated with ERV activity in humans, adaptive immune responses to ERV-encoded gene products remain poorly defined and have not been investigated in the physiologically relevant non-human primate model of human disease. FINDINGS: Here, we identified the rhesus macaque equivalent of the biologically active human ERV-K (HML-2), simian ERV-K (SERV-K1), which retains intact open reading frames for both Gag and Env on chromosome 12 in the macaque genome. From macaque cells we isolated a spliced mRNA product encoding SERV-K1 Env, which possesses all the structural features of a canonical, functional retroviral Envelope protein. Furthermore, we identified rare, but robust T cell responses as well as frequent antibody responses targeting SERV-K1 Env in rhesus macaques. CONCLUSIONS: These data demonstrate that SERV-K1 retains biological activity sufficient to induce cellular and humoral immune responses in rhesus macaques. As ERV-K is the youngest and most active ERV family in the human genome, the identification and characterization of the simian orthologue in rhesus macaques provides a highly relevant animal model in which to study the role of ERV-K in developmental and disease states.


Assuntos
Anticorpos Antivirais/sangue , Retrovirus Endógenos/imunologia , Produtos do Gene env/imunologia , Linfócitos T/imunologia , Animais , Retrovirus Endógenos/genética , Feminino , Produtos do Gene env/genética , Macaca mulatta , Masculino , Dados de Sequência Molecular , Análise de Sequência de DNA
2.
Proc Natl Acad Sci U S A ; 106(24): 9791-6, 2009 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-19478057

RESUMO

The precise immunological role played by CD4(+) T cells in retroviral infections is poorly defined. Here, we describe a new function of these cells, the elimination of retrovirus-infected macrophages. After experimental CD8(+) cell depletion, elite controlling macaques with set-point viral loads < or = 500 viral RNA copies/mL mounted robust Gag- and Nef-specific CD4(+) T cell responses during reestablishment of control with > or = 54% of all virus-specific CD4(+) T cells targeting these 2 proteins. Ex vivo, these simian immunodeficiency virus (SIV)-specific CD4(+) T cells neither recognized nor suppressed viral replication in SIV-infected CD4(+) T cells. In contrast, they recognized SIV-infected macrophages as early as 2 h postinfection because of presentation of epitopes derived from virion-associated Gag and Nef proteins. Furthermore, virus-specific CD4(+) T cells displayed direct effector function and eliminated SIV-infected macrophages. These results suggest that retrovirus-specific CD4(+) T cells may contribute directly to elite control by inhibiting viral replication in macrophages.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Produtos do Gene gag/metabolismo , Produtos do Gene nef/metabolismo , Macrófagos/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/fisiologia , Replicação Viral/imunologia , Animais , Linfócitos T CD4-Positivos/metabolismo , Macaca mulatta , RNA Viral/sangue , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/isolamento & purificação , Carga Viral
3.
Genes (Basel) ; 13(12)2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36553566

RESUMO

White mold can result in snap bean yield losses of 90 to 100% when field conditions favor the pathogen. A genome-wide association study (GWAS) was conducted to detect loci significantly associated with white mold resistance in a panel of snap bean (Phaseolus vulgaris L.) cultivars. Two populations of snap bean were used in this study. The first population was the BeanCAP (Coordinated Agriculture Project) Snap Bean Diversity Panel (SBDP) (n = 136), and the second population was the Snap Bean Association Panel (SnAP) (n = 378). SBDP was evaluated for white mold reaction in the field in 2012 and 2013, and SnAP was screened in a greenhouse only using the seedling straw test in 2016. Two reference genomes representing the Andean and Middle American centers of domestication were utilized to align the genotyping-by-sequencing (GBS) data. A GWAS was performed using FarmCPU with one principal component after comparing five models. Thirty-four single-nucleotide polymorphisms (SNPs) significantly associated with white mold resistance were detected. Eleven significant SNPs were identified by the seedling straw test, and 23 significant SNPs were identified by field data. Fifteen SNPs were identified within a 100 kb window containing pentatricopeptide repeat (PPR)-encoding genes, and eleven were close to leucine-rich repeat (LRR)-encoding genes, suggesting that these two classes are of outsized importance for snap bean resistance to white mold.


Assuntos
Estudo de Associação Genômica Ampla , Phaseolus , Estados Unidos , Phaseolus/genética , Fungos/genética , Agricultura
4.
J Virol ; 84(20): 10907-12, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20686015

RESUMO

The kinetics of CD8(+) T cell epitope presentation contribute to the antiviral efficacy of these cells yet remain poorly defined. Here, we demonstrate presentation of virion-derived Vpr peptide epitopes early after viral penetration and prior to presentation of Vif-derived epitopes, which required de novo Vif synthesis. Two Rev epitopes exhibited differential presentation kinetics, with one Rev epitope presented within 1 h of infection. We also demonstrate that cytolytic activity mirrors the recognition kinetics of infected cells. These studies show for the first time that Vpr- and Rev-specific CD8(+) T cells recognize and kill simian immunodeficiency virus (SIV)-infected CD4(+) T cells early after SIV infection.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Produtos do Gene rev/imunologia , Produtos do Gene vpr/imunologia , Vírus da Imunodeficiência Símia/imunologia , Sequência de Aminoácidos , Animais , Apresentação de Antígeno , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Citotoxicidade Imunológica , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Produtos do Gene rev/genética , Produtos do Gene vpr/genética , Interações Hospedeiro-Patógeno/imunologia , Técnicas In Vitro , Cinética , Macaca mulatta , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/enzimologia , Vírus da Imunodeficiência Símia/patogenicidade , Vírus da Imunodeficiência Símia/fisiologia
5.
Front Plant Sci ; 12: 697615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650574

RESUMO

Root rot is a major constraint to snap bean (Phaseolus vulgaris) production in the United States and around the world. Genetic resistance is needed to effectively control root rot disease because cultural control methods are ineffective, and the pathogen will be present at the end of one season of production on previously clean land. A diversity panel of 149 snap bean pure lines was evaluated for resistance to Fusarium root rot in Oregon. Morphological traits potentially associated with root rot resistance, such as aboveground biomass, adventitious roots, taproot diameter, basal root diameter, deepest root angle, shallowest root angle, root angle average, root angle difference, and root angle geometric mean were evaluated and correlated to disease severity. A genome wide association study (GWAS) using the Fixed and random model Circulating Probability Unification (FarmCPU) statistical method, identified five associated single nucleotide polymorphisms (SNPs) for disease severity and two SNPs for biomass. The SNPs were found on Pv03, Pv07, Pv08, Pv10, and Pv11. One candidate gene for disease reaction near a SNP on Pv03 codes for a peroxidase, and two candidates associated with biomass SNPs were a 2-alkenal reductase gene cluster on Pv10 and a Pentatricopeptide repeat domain on Pv11. Bean lines utilized in the study were ranked by genomic estimated breeding values (GEBV) for disease severity, biomass, and the root architecture traits, and the observed and predicted values had high to moderate correlations. Cross validation of genomic predictions showed slightly lower correlational accuracy. Bean lines with the highest GEBV were among the most resistant, but did not necessarily rank at the very top numerically. This study provides information on the relationship of root architecture traits to root rot disease reaction. Snap bean lines with genetic merit for genomic selection were identified and may be utilized in future breeding efforts.

6.
Immunogenetics ; 62(10): 701-7, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20812010

RESUMO

We recently demonstrated that vaccinated rhesus macaques controlled viral replication of a heterologous SIV challenge. Here, we analyzed anamnestic SIV-specific CD4+ T-cell responses expanding immediately after challenge and show that successful vaccinees consistently targeted a short region of the Gag-p27 Capsid (amino acids 249-291). We have also defined the major histocompatibility complex class II (MHC-II) restricting alleles for several of these responses and show that DQ-restricted CD4+ T-cells depend on unique combinations of both the DQA and DQB alleles. Analysis of SIV-specific CD4+ T-cell responses elicited by a successful vaccine may have important implications in the understanding of vaccine design.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Produtos do Gene gag/imunologia , Macaca mulatta/imunologia , Vacinas contra a SAIDS/imunologia , Vírus da Imunodeficiência Símia/imunologia , Subpopulações de Linfócitos T/imunologia , Sequência de Aminoácidos , Animais , Epitopos/imunologia , Genes MHC da Classe II , Antígenos de Histocompatibilidade Classe II/imunologia , Memória Imunológica , Macaca mulatta/genética , Dados de Sequência Molecular , Fragmentos de Peptídeos/imunologia , Proteínas dos Retroviridae/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Vírus da Imunodeficiência Símia/isolamento & purificação , Vírus da Imunodeficiência Símia/fisiologia , Vacinação , Carga Viral , Viremia/imunologia , Viremia/prevenção & controle , Replicação Viral
7.
J Virol ; 83(12): 6011-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19339351

RESUMO

Vaccines that elicit CD8(+) T-cell responses are routinely tested for immunogenicity in nonhuman primates before advancement to clinical trials. Unfortunately, the magnitude and specificity of vaccine-elicited T-cell responses are variable in currently utilized nonhuman primate populations, owing to heterogeneity in major histocompatibility (MHC) class I genetics. We recently showed that Mauritian cynomolgus macaques (MCM) have unusually simple MHC genetics, with three common haplotypes encoding a shared pair of MHC class IA alleles, Mafa-A*25 and Mafa-A*29. Based on haplotype frequency, we hypothesized that CD8(+) T-cell responses restricted by these MHC class I alleles would be detected in nearly all MCM. We examine here the frequency and functionality of these two alleles, showing that 88% of MCM express Mafa-A*25 and Mafa-A*29 and that animals carrying these alleles mount three newly defined simian immunodeficiency virus-specific CD8(+) T-cell responses. The epitopes recognized by each of these responses accumulated substitutions consistent with immunologic escape, suggesting these responses exert antiviral selective pressure. The demonstration that Mafa-A*25 and Mafa-A*29 restrict CD8(+) T-cell responses that are shared among nearly all MCM indicates that these animals are an advantageous nonhuman primate model for comparing the immunogenicity of vaccines that elicit CD8(+) T-cell responses.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Antígenos de Histocompatibilidade Classe I/genética , Macaca fascicularis/genética , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Alelos , Substituição de Aminoácidos , Animais , Antígenos Virais/genética , Antígenos Virais/imunologia , Linfócitos T CD8-Positivos/virologia , Epitopos de Linfócito T/imunologia , Frequência do Gene , Haplótipos , Antígenos de Histocompatibilidade Classe I/imunologia , Macaca fascicularis/imunologia , Repetições de Microssatélites , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia
8.
J Virol ; 82(18): 9293-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18596093

RESUMO

The kinetics of peptide presentation by major histocompatibility complex class I (MHC-I) molecules may contribute to the efficacy of CD8+ T cells. Whether all CD8+ T-cell epitopes from a protein are presented by the same MHC-I molecule with similar kinetics is unknown. Here we show that CD8+ T-cell epitopes derived from SIVmac239 Gag are presented with markedly different kinetics. We demonstrate that this discrepancy in presentation is not related to immunodominance but instead is due to differential requirements for epitope generation. These results illustrate that significant differences in presentation kinetics can exist among CD8+ T-cell epitopes derived from the same viral protein.


Assuntos
Apresentação de Antígeno/fisiologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T/imunologia , Produtos do Gene gag/imunologia , Antígenos de Histocompatibilidade Classe I/metabolismo , Vírus da Imunodeficiência Símia/metabolismo , Animais , Células Apresentadoras de Antígenos , Epitopos de Linfócito T/química , Epitopos de Linfócito T/metabolismo , Antígenos de Histocompatibilidade Classe I/imunologia , Epitopos Imunodominantes , Cinética , Vírus da Imunodeficiência Símia/imunologia
9.
J Virol ; 82(2): 859-70, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17989178

RESUMO

The role of CD4(+) T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4(+) T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4(+) T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4(+) T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-II alleles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (P value of <0.0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4(+) T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.


Assuntos
Frequência do Gene , Antígenos HLA-DR/genética , Síndrome de Imunodeficiência Adquirida dos Símios/genética , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Carga Viral , Animais , Linfócitos T CD4-Positivos/imunologia , Predisposição Genética para Doença , Macaca mulatta , RNA Viral/sangue
10.
Nutrients ; 11(10)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31635241

RESUMO

Snap beans are a significant source of micronutrients in the human diet. Among the micronutrients present in snap beans are phenolic compounds with known beneficial effects on human health, potentially via their metabolism by the gut-associated microbiome. The genetic pathways leading to the production of phenolics in snap bean pods remain uncertain. In this study, we quantified the level of total phenolic content (TPC) in the Bean Coordinated Agriculture Program (CAP) snap bean diversity panel of 149 accessions. The panel was characterized spectrophotometrically for phenolic content with a Folin-Ciocalteu colorimetric assay. Flower, seed and pod color were also quantified, as red, purple, yellow and brown colors are associated with anthocyanins and flavonols in common bean. Genotyping was performed through an Illumina Infinium Genechip BARCBEAN6K_3 single nucleotide polymorphism (SNP) array. Genome-Wide Association Studies (GWAS) analysis identified 11 quantitative trait nucleotides (QTN) associated with TPC. An SNP was identified for TPC on Pv07 located near the P gene, which is a major switch in the flavonoid biosynthetic pathway. Candidate genes were identified for seven of the 11 TPC QTN. Five regulatory genes were identified and represent novel sources of variation for exploitation in developing snap beans with higher phenolic levels for greater health benefits to the consumer.


Assuntos
Estudo de Associação Genômica Ampla , Phaseolus/genética , Phaseolus/metabolismo , Fenóis/metabolismo , Regulação da Expressão Gênica de Plantas , Marcadores Genéticos , Variação Genética , Genótipo , Humanos , Phaseolus/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Sementes
11.
Mamm Genome ; 19(4): 263-71, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18379846

RESUMO

Previous studies on the fourth inversion of the t complex, In17(4), suggest that loci near the center of this inversion have been subjected to segmental recombination during the past 1-2 million years. We have used a combination of PCR-based restriction site (PBR) analysis and DNA sequencing to perform a high-resolution analysis of a 2-million base pair (Mbp) segment in the middle of In17(4). We examined 21 restriction sites that are polymorphic between t haplotypes and their wild-type homologs, over nine distinct loci. In addition, we examined several other polymorphic sites through DNA sequence analysis of two of these nine loci. We analyzed several haplotypes in this way, including the "complete" t haplotypes tw2, t0, tw32, tw71, and tw75. We show that only tw32 is a true "complete" t haplotype; the remaining four t haplotypes have segments of wild-type DNA ranging from less than 100 bp to 2 Mbp. The sizes of these wild-type DNA segments are consistent with their being generated by gene-conversion events. The 2-Mbp segment is located in a region that may contain the t-complex distorter gene Tcd2. One of the nine loci examined in this study is Fgd2, a gene that has been proposed to encode Tcd2. Sequencing and PBR data show that at least a portion of the Fgd2 gene has been converted to the wild-type within tw71 and tw75mice.


Assuntos
Haplótipos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Nucleares/genética , Recombinação Genética , Animais , Sequência de Bases , Cromossomos de Mamíferos , Genoma , Fatores de Troca do Nucleotídeo Guanina/genética , Masculino , Camundongos , Camundongos Endogâmicos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA , Região do Complexo-t do Genoma
12.
PLoS One ; 2(11): e1152, 2007 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-18000532

RESUMO

BACKGROUND: It is generally accepted that CD8+ T cell responses play an important role in control of immunodeficiency virus replication. The association of HLA-B27 and -B57 with control of viremia supports this conclusion. However, specific correlates of viral control in individuals expressing these alleles have been difficult to define. We recently reported that transient in vivo CD8+ cell depletion in simian immunodeficiency virus (SIV)-infected elite controller (EC) macaques resulted in a brief period of viral recrudescence. SIV replication was rapidly controlled with the reappearance of CD8+ cells, implicating that these cells actively suppress viral replication in ECs. METHODS AND FINDINGS: Here we show that three ECs in that study made at least seven robust CD8+ T cell responses directed against novel epitopes in Vif, Rev, and Nef restricted by the MHC class I molecule Mamu-B*08. Two of these Mamu-B*08-positive animals subsequently lost control of SIV replication. Their breakthrough virus harbored substitutions in multiple Mamu-B*08-restricted epitopes. Indeed, we found evidence for selection pressure mediated by Mamu-B*08-restricted CD8+ T cells in all of the newly identified epitopes in a cohort of chronically infected macaques. CONCLUSIONS: Together, our data suggest that Mamu-B*08-restricted CD8+ T cell responses effectively control replication of pathogenic SIV(mac)239. All seven regions encoding Mamu-B*08-restricted CD8+ T cell epitopes also exhibit amino acid replacements typically seen only in the presence of Mamu-B*08, suggesting that the variation we observe is indeed selected by CD8+ T cell responses. SIV(mac)239 infection of Indian rhesus macaques expressing Mamu-B*08 may therefore provide an animal model for understanding CD8+ T cell-mediated control of HIV replication in humans.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Epitopos/imunologia , Variação Genética , Vírus da Imunodeficiência Símia/imunologia , Animais , Sequência de Bases , Linfócitos T CD8-Positivos/virologia , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Macaca mulatta , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , RNA Viral/genética , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/fisiologia , Replicação Viral
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