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1.
PLoS Pathog ; 19(3): e1011209, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36897929

RESUMEN

CD4+ tissue resident memory T cells (TRMs) are implicated in the formation of persistent HIV reservoirs that are established during the very early stages of infection. The tissue-specific factors that direct T cells to establish tissue residency are not well defined, nor are the factors that establish viral latency. We report that costimulation via MAdCAM-1 and retinoic acid (RA), two constituents of gut tissues, together with TGF-ß, promote the differentiation of CD4+ T cells into a distinct subset α4ß7+CD69+CD103+ TRM-like cells. Among the costimulatory ligands we evaluated, MAdCAM-1 was unique in its capacity to upregulate both CCR5 and CCR9. MAdCAM-1 costimulation rendered cells susceptible to HIV infection. Differentiation of TRM-like cells was reduced by MAdCAM-1 antagonists developed to treat inflammatory bowel diseases. These finding provide a framework to better understand the contribution of CD4+ TRMs to persistent viral reservoirs and HIV pathogenesis.


Asunto(s)
Linfocitos T CD4-Positivos , Infecciones por VIH , Humanos , Factor de Crecimiento Transformador beta , Tretinoina/farmacología , Diferenciación Celular , Memoria Inmunológica , Receptores CCR5
2.
PLoS Pathog ; 19(12): e1011860, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38064524

RESUMEN

The CD4 receptor, by stabilizing TCR-MHC II interactions, plays a central role in adaptive immunity. It also serves as the HIV docking receptor. The HIV gp120 envelope protein binds directly to CD4. This interaction is a prerequisite for viral entry. gp120 also binds to ⍺4ß7, an integrin that is expressed on a subset of memory CD4+ T cells. HIV tropisms for CD4+ T cells and gut tissues are central features of HIV pathogenesis. We report that CD4 binds directly to ⍺4ß7 in a dynamic way, consistent with a cis regulatory interaction. The molecular details of this interaction are related to the way in which gp120 interacts with both receptors. Like MAdCAM-1 and VCAM-1, two recognized ligands of ⍺4ß7, the binding interface on CD4 includes 2 sites (1° and accessory), distributed across its two N-terminal IgSF domains (D1 and D2). The 1° site includes a sequence in the G ß-strand of CD4 D2, KIDIV, that binds directly to ⍺4ß7. This pentapeptide sequence occurs infrequently in eukaryotic proteins. However, a closely related and conserved sequence, KLDIV, appears in the V2 domain of gp120. KLDIV mediates gp120-⍺4ß7 binding. The accessory ⍺4ß7 binding site on CD4 includes Phe43. The Phe43 aromatic ring protrudes outward from one edge of a loop connecting the C'C" strands of CD4 D1. Phe43 is a principal contact for HIV gp120. It interacts with conserved residues in the recessed CD4 binding pocket. Substitution of Phe43 abrogates CD4 binding to both gp120 and ⍺4ß7. As such, the interactions of gp120 with both CD4 and ⍺4ß7 reflect elements of their interactions with each other. These findings indicate that gp120 specificities for CD4 and ⍺4ß7 are interrelated and suggest that selective pressures which produced a CD4 tropic virus that replicates in gut tissues are linked to a dynamic interaction between these two receptors.


Asunto(s)
Infecciones por VIH , Integrinas , Humanos , Integrinas/metabolismo , Sitios de Unión , Antígenos CD4 , Linfocitos T CD4-Positivos/metabolismo , Proteína gp120 de Envoltorio del VIH/metabolismo
3.
BMC Bioinformatics ; 25(1): 125, 2024 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-38519883

RESUMEN

In the battle of the host against lentiviral pathogenesis, the immune response is crucial. However, several questions remain unanswered about the interaction with different viruses and their influence on disease progression. The simian immunodeficiency virus (SIV) infecting nonhuman primates (NHP) is widely used as a model for the study of the human immunodeficiency virus (HIV) both because they are evolutionarily linked and because they share physiological and anatomical similarities that are largely explored to understand the disease progression. The HIHISIV database was developed to support researchers to integrate and evaluate the large number of transcriptional data associated with the presence/absence of the pathogen (SIV or HIV) and the host response (NHP and human). The datasets are composed of microarray and RNA-Seq gene expression data that were selected, curated, analyzed, enriched, and stored in a relational database. Six query templates comprise the main data analysis functions and the resulting information can be downloaded. The HIHISIV database, available at  https://hihisiv.github.io , provides accurate resources for browsing and visualizing results and for more robust analyses of pre-existing data in transcriptome repositories.


Asunto(s)
Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Humanos , Virus de la Inmunodeficiencia de los Simios/genética , VIH , Síndrome de Inmunodeficiencia Adquirida del Simio/genética , Progresión de la Enfermedad , Inmunidad , Expresión Génica
4.
J Antimicrob Chemother ; 78(6): 1444-1453, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37039023

RESUMEN

BACKGROUND: Antiretroviral therapy has revolutionized HIV treatment, increasing quality and life expectancy of people living with HIV (PLWH). However, the expansion of treatment has resulted in an increase in antiretroviral-resistant viruses, which can be an obstacle to maintenance of successful ART. OBJECTIVES: This study analysed the genetic composition of the HIV near full-length genome (NFLG) from archived proviruses of PLWH under successful ART, and determined the presence/frequency of drug resistance mutations (DRMs) and viral subtype. PATIENTS AND METHODS: Forty-six PLWH from Rio de Janeiro (RJ) and 40 from Rio Grande (RS) had proviral HIV NFLG PCR-amplified and ultradeep sequenced. The presence/frequency of DRMs were analysed in Geneious. Phylogenetic analyses were performed using PhyML and SimPlot. RESULTS: All samples included in the study were sequenced and 69 (80.2%) had the HIV NFLG determined. RJ and RS showed a predominance of HIV subtypes B (78.3%) and C (67.5%), respectively. Overall, 168 DRMs were found in 63 (73.3%) samples, and 105 (62.5%) of them were minority variants. Among DRMs, 41 (39.0%) minority variants and 33 (52.4%) variants with frequency above 20.0% in the viral population were able to confer some degree of resistance to at least one drug in use by respective patients, yet no one showed signs of therapeutic failure. CONCLUSIONS: Our study contributes to the understanding of the impact of DRMs on successful therapy and supports the sustainability of combinatorial ART, because all patients maintained their successful treatment despite the high prevalence of DRMs at low (62.5%) or high (37.5%) frequency.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Filogenia , Brasil/epidemiología , Antirretrovirales/farmacología , Antirretrovirales/uso terapéutico , Seropositividad para VIH/tratamiento farmacológico , Mutación , Provirus/genética , Farmacorresistencia Viral/genética , Genotipo , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico
5.
Proc Natl Acad Sci U S A ; 117(51): 32566-32573, 2020 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-33288704

RESUMEN

Acute HIV infection is characterized by rapid viral seeding of immunologic inductive sites in the gut followed by the severe depletion of gut CD4+ T cells. Trafficking of α4ß7-expressing lymphocytes to the gut is mediated by MAdCAM, the natural ligand of α4ß7 that is expressed on gut endothelial cells. MAdCAM signaling through α4ß7 costimulates CD4+ T cells and promotes HIV replication. Similar to MAdCAM, the V2 domain of the gp120 HIV envelope protein binds to α4ß7 In this study, we report that gp120 V2 shares with MAdCAM the capacity to signal through α4ß7 resulting in CD4+ T cell activation and proliferation. As with MAdCAM-mediated costimulation, cellular activation induced by gp120 V2 is inhibited by anti-α4ß7 monoclonal antibodies (mAbs). It is also inhibited by anti-V2 domain antibodies including nonneutralizing mAbs that recognize an epitope in V2 that has been linked to reduced risk of acquisition in the RV144 vaccine trial. The capacity of the V2 domain of gp120 to mediate signaling through α4ß7 likely impacts early events in HIV infection. The capacity of nonneutralizing V2 antibodies to block this activity reveals a previously unrecognized mechanism whereby such antibodies might impact HIV transmission and pathogenesis.


Asunto(s)
Linfocitos T CD4-Positivos/virología , Proteína gp120 de Envoltorio del VIH/metabolismo , Infecciones por VIH/metabolismo , Integrinas/metabolismo , Fármacos Anti-VIH/inmunología , Fármacos Anti-VIH/farmacología , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/farmacología , Anticuerpos Neutralizantes/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Proliferación Celular , Epítopos/inmunología , Epítopos/metabolismo , Proteína gp120 de Envoltorio del VIH/química , Proteína gp120 de Envoltorio del VIH/inmunología , Infecciones por VIH/patología , Infecciones por VIH/virología , Interacciones Huésped-Patógeno/fisiología , Humanos , Activación de Linfocitos , Dominios Proteicos , Transducción de Señal , Virus de la Inmunodeficiencia de los Simios/inmunología , Tretinoina/farmacología
6.
Am J Dent ; 36(4): 188-192, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37587029

RESUMEN

PURPOSE: To evaluate the smoothness provided by a one-step finishing and polishing system and its maintenance after hydrothermal aging and brushing of a nanofilled resin composite. METHODS: 96 samples of the nanofilled composite Filtek Z350 XT were fabricated, which, after initial average roughness (Ra) analysis, were randomly distributed into three groups, according to the selected finishing and polishing system. The multi-step systems Sof-Lex (aluminum oxide discs) and Jiffy (bullet-shaped abrasive rubbers), and the one-step system OneGloss (bullet-shaped abrasive rubber) were used. After finishing and polishing, a new Ra measurement was performed, and then half of the samples from each group were stored in artificial saliva for 12 months, while the other half underwent aging processes associating hydrothermal cycles (10,000 cycles at 5-55°C) followed by brushing (5,500 strokes), with a mid-abrasive (Crest Cavity Protection) dentifrice slurry, simulating a 12-month period in the oral cavity. Final Ra measurements were performed, and data were analyzed by generalized linear model and Tukey's test (α= 5%). RESULTS: There was interaction between finishing and polishing system and aging (P< 0.001). The one-step abrasive rubber point provided significantly higher Ra values compared to the multi-step systems, and with the discs there was higher smoothness than with the rubber point sequence. This result was maintained after 12 months in artificial saliva, but after hydrothermal cycles followed by brushing, one-step and multi-step abrasive rubber points no longer significantly differed from each other. Only for the one-step system, hydrothermal cycles followed by brushing significantly reduced Ra. CLINICAL SIGNIFICANCE: Although hydrothermal cycles followed by brushing may have increased the smoothness of nanofilled composite finished and polished with the one-step system, only the multi-step system provided a surface within the roughness threshold to avoid biofilm retention.


Asunto(s)
Caries Dental , Goma , Humanos , Biopelículas , Instrumentos Dentales , Saliva Artificial
7.
Int J Food Sci Nutr ; 74(6): 655-667, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37612883

RESUMEN

Millions of dollars have been increasingly spent on plant-based diets. Considering that vitamin B12 is obtained from the consumption of animal-derived foods, new sources of vitamin B12 and methods of food fortification are being eagerly sought. Therefore, this work aims to evaluate advances in situ fermentation processes of food and beverages produced on a large scale and industrial applications for obtaining cobalamin-rich products. Bibliometric analysis was performed and revealed that several studies report a great capacity for in situ biofortification of B12 in foods, mostly on the use of propionic (PB) and lactic (LAB) bacteria. In this context, market potentials for such products, the main microorganisms, including simultaneous cultures, and their respective applications have been presented herein. Although knowledge on potential applications is still limited, field research has been increasingly conducted, thus revealing scientific and technological opportunities, both for the production and the stability of B12 found in plant-based foods.


Asunto(s)
Alimentos Fermentados , Vitamina B 12 , Animales , Biofortificación , Bebidas , Alimentación Animal
8.
J Environ Manage ; 340: 117954, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37119623

RESUMEN

After successful invasions in the Caribbean and Mediterranean, lionfish (Pterois spp.) have recently invaded another important biogeographical region -the Brazilian Province. In this article, we discuss this new invasion, focusing on a roadmap for urgent mitigation of the problem, as well as focused research and management strategies. The invasion in Brazil is already in the consolidation stage, with 352 individuals recorded so far (2020-2023) along 2766 km of coastline. This includes both juveniles and adults, including egg-bearing females, ranging in length from 9.1 to 38.5 cm. Until now, most of the records in the Brazilian coast occurred in the equatorial southwestern Atlantic (99%), mainly on the Amazon mesophotic reefs (15% of the records), northeastern coast of Brazil (45%), and the Fernando de Noronha Archipelago (41%; an UNESCO World Heritage Site with high endemism rate). These records cover a broad depth range (1-110 m depth), twelve protected areas, eight Brazilian states (Amapá, Pará, Maranhão, Piauí, Ceará, Rio Grande do Norte, Paraíba, and Pernambuco) and multiple habitats (i.e., mangrove estuaries, shallow-water and mesophotic reefs, seagrass beds, artificial reefs, and sandbanks), indicating a rapid and successful invasion process in Brazilian waters. In addition, the lack of local knowledge of rare and/or cryptic native species that are potentially vulnerable to lionfish predation raises concerns regarding the potential overlooked ecological impacts. Thus, we call for an urgent integrated approach with multiple stakeholders and solution-based ecological research, real-time inventories, update of environmental and fishery legislation, participatory monitoring supported by citizen science, and a national and unified plan aimed at decreasing the impact of lionfish invasion. The experience acquired by understanding the invasion process in the Caribbean and Mediterranean will help to establish and prioritize goals for Brazil.


Asunto(s)
Ecosistema , Perciformes , Humanos , Animales , Brasil , Región del Caribe , Conducta Predatoria , Especies Introducidas
9.
Genet Mol Biol ; 46(4): e20230015, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38051353

RESUMEN

A complete genome of the first anellovirus infecting the wild felid Leopardus pardalis (ocelot) and a partial genome were assembled and annotated through high-throughput sequencing protocols followed by Sanger sequencing validation. The full-length virus obtained comprises 2,003 bp, while the partial genome comprises 1,224 bp. Phylogenetic analysis grouped these two sequences in two distinct clusters related to previously described Felidae anelloviruses. The ORF1 of the partial genome was identified as a new species provisionally called Torque teno ocelot virus, with 53.6% identity with its sister lineage. The complete genome was inferred as a new representative of the Torque teno felid virus 3 species, with 73.28% identity to the closest reference. This study expands known virus diversity and the host span of anelloviruses.

10.
J Antimicrob Chemother ; 76(3): 639-647, 2021 02 11.
Artículo en Inglés | MEDLINE | ID: mdl-33184634

RESUMEN

OBJECTIVES: The development of HIV drug resistance against the integrase strand transfer inhibitor dolutegravir is rare. We report here the transient detection, by near full-genome ultradeep sequencing, of minority HIV-1 subtype B variants bearing the S153F and R263K integrase substitutions in the proviral DNA from blood cells of one patient who successfully initiated dolutegravir-based ART, over 24 weeks. Our objective was to study the effects of these substitutions. METHODS: Strand transfer and DNA-binding activities of recombinant integrase proteins were measured in cell-free assays. Cell-based resistance, infectivity and replicative capacities were measured using molecular clones. Structural modelling was performed to understand experimental results. RESULTS: R263K emerged first, followed by the addition of S153F at Week 12. By Week 24, both mutations remained present, but at lower prevalence. We confirmed the coexistence of S153F and R263K on single viral genomes. Combining S153F or S153Y with R263K decreased integration and viral replicative capacity and conferred high levels of drug resistance against all integrase inhibitors. Alone, S153Y and S153F did little to infectivity or dolutegravir resistance. We identified altered DNA binding as a mechanism of resistance. The patient remained with undetectable viral loads at all timepoints. CONCLUSIONS: Drug-resistant minority variants have often been reported under suppressive ART. Our study adds to these observations by unravelling a progression towards higher levels of resistance through a novel pathway despite continuous undetectable viral loads. Poorly replicative HIV drug-resistant minority proviral variants did not compromise viral suppression in one individual treated with dolutegravir.


Asunto(s)
Infecciones por VIH , Inhibidores de Integrasa VIH , Integrasa de VIH , VIH-1 , Sustitución de Aminoácidos , ADN , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Integrasa de VIH/genética , Inhibidores de Integrasa VIH/farmacología , Inhibidores de Integrasa VIH/uso terapéutico , VIH-1/genética , Compuestos Heterocíclicos con 3 Anillos/farmacología , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Humanos , Mutación , Oxazinas/farmacología , Piperazinas/farmacología , Provirus/genética , Piridonas/farmacología
11.
An Acad Bras Cienc ; 93(4): e20190543, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34730669

RESUMEN

Agriculture needs methodologies that assist in the determination of soil attributes and variability mapping attributes with greater levels of detail. Therefore, the objective of this research was to evaluate magnetic susceptibility as auxiliary variable for estimating soil attributes in areas of Indian Black Earths in the south of Amazonas State. Three Indian Black Earth areas are located in the municipalities of Apuí and Manicoré - Amazonas, under uses with coffee, cocoa and pasture. The soils were collected at the crossing points in the depth of 0.00 - 0.20 m, making a total of 88 sampling points/area, and totaling 264 samples. The points were georeferenced for geostatistical modeling. After that, physical and chemical analyzes were performed to obtain the values ​​of soil and magnetic susceptibility attributes. Descriptive statistics, Pearson correlation, linear regression and geostatistical analyzes were applied for Pedotransfer Function modeling and the spatial variability of the analyzed attributes. Magnetic susceptibility showed a high degree of spatial dependence in the study areas, high range values, correlating with most of the assessed attributes, mainly physical, indicating potential in the prediction of the attributes in these environments. Pedotransfer functions vary among IBE's sites in attribute prediction, ensuring moderate estimates for predicting soil attributes in IBE's areas.


Asunto(s)
Contaminantes del Suelo , Suelo , Agricultura , Brasil , Monitoreo del Ambiente , Contaminantes del Suelo/análisis , Análisis Espacial
12.
Fam Pract ; 37(5): 648-654, 2020 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-32297637

RESUMEN

BACKGROUND: Primary health care (PHC) delivery in Brazil has improved in the last decades. However, it remains unknown whether the Family Health Strategy teams are meeting the health needs of the population. OBJECTIVES: To describe the reasons for encounter (RFEs) in PHC in Brazil and to examine variations in RFEs according to sex, age and geographic region. METHODS: This descriptive study is part of a national cross-sectional study conducted in 2016. The sample was stratified by the number of PHC physicians per geographic region. Physicians who had been working for at least 1 year in the same PHC unit were included. For every participating physician, 12 patients aged ≥18 years who had attended at least two encounters were included. Patients were asked about their RFEs, which were classified according to the International Classification of Primary Care. RESULTS: In 6160 encounters, a total of 8046 RFEs were coded. Seven reasons accounted for 50% of all RFEs. There was a high frequency of codes related to test results, medication renewal and preventive medicine. RFEs did not vary significantly by sex or geographic region, but they did by age group (P < 0.001). The rates of prescriptions, requests for investigations and referrals to specialized care were 71.1%, 42.8%, and 21.3%, respectively. CONCLUSION: This novel study opened the 'black box' of RFEs in PHC in Brazil. These findings can contribute to redefining the scope of PHC services and reorienting work practices in order to improve the quality of PHC in Brazil.


Asunto(s)
Médicos de Atención Primaria , Atención Primaria de Salud , Adolescente , Adulto , Brasil , Estudios Transversales , Humanos , Derivación y Consulta
13.
Mem Inst Oswaldo Cruz ; 115: e200153, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32785421

RESUMEN

In an enclosure with nine collared peccaries (Pecari tajacu) from the Rio de Janeiro city Zoo, Brazil, one specimen was found dead and two others developed prostration, apathy and dehydration, resulting on its death. Necropsy of two animals pointed to pulmonary and renal damage. Histological examination revealed vasculitis in spleen from both P. tajacu, suggesting a systemic viral infection. Lungs from one specimen showed fibrinoid vasculitis, alveolar damage with hyaline membrane, and interstitial lymphocytes infiltration. Virome analysis in anal wash samples from the latter two animals revealed a new type of Betacoronavirus, lineage A, provisionally named Ptajacu-CoV.


Asunto(s)
Artiodáctilos/virología , Betacoronavirus/aislamiento & purificación , Animales , Betacoronavirus/genética , Brasil , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/mortalidad
14.
J Med Virol ; 91(1): 31-37, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30133818

RESUMEN

Recent studies have suggested that human pegivirus 1 (HPgV-1) may have some pathogenic potential. In the southernmost region of Brazil, studies on HPgV-1 are scarce, and circulating genotypes have not yet been identified. The current study aimed to evaluate the prevalence of HPgV-1 among blood donors from the southernmost region of Brazil and identify the genotypes involved with associated factors. A cross-sectional study was conducted with 281 blood donors, who had their plasma subjected to RNA extraction, complementary DNA synthesis, HPgV-1 detection by nested polymerase chain reaction, and subsequent genotyping. The observed prevalence of HPgV-1-RNA was 21.7%. The only variable that was significantly associated with virus infection was the relationship status of the donor. Single or no fixed partner blood donors were twice as likely to have HPgV-1 (95% CI, 1.12 to 4.56; P = 0.02). Genotype 2-subtypes 2b (69%) and 2a (29%)-was the most prevalent. In the absence of risk factors for parenteral transmission, it is likely that sexual transmission was the route of infection in the individuals studied. Further work will be needed to determine whether this virus is inert in the population, or if there are potential deleterious effects in infected individuals.


Asunto(s)
Donantes de Sangre , Transmisión de Enfermedad Infecciosa , Infecciones por Flaviviridae/epidemiología , Infecciones por Flaviviridae/transmisión , Flaviviridae/aislamiento & purificación , Genotipo , Adolescente , Adulto , Brasil/epidemiología , Estudios Transversales , Femenino , Flaviviridae/clasificación , Flaviviridae/genética , Técnicas de Genotipaje , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Adulto Joven
15.
AIDS Res Ther ; 16(1): 19, 2019 08 14.
Artículo en Inglés | MEDLINE | ID: mdl-31412889

RESUMEN

Brazil is a low-and-middle income country (LMIC) that, despite having a large population and continental dimensions, has been able to successfully fight HIV/AIDS through a number of governmental and societal measures. These included an early response to the epidemic, the development of a universal and free public health system, incisive discussions with pharmaceutical companies to reduce antiretroviral (ARV) drug prices, investments towards the development of generic drugs and compulsory licensing of ARVs. Through such measures, Brazil is among the leading LMIC towards achieving the 90-90-90 UNAIDS goals in the years to come. In this review, we analyze Brazil's progress throughout the HIV/AIDS epidemic to achieve state-of-the-art ARV treatment and to reduce AIDS mortality in the country. The top-quality HIV/AIDS research in Brazil towards HIV prophylactic and functional cure, the next step towards the economic sustainability of the battle against HIV, is also discussed.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/economía , Antirretrovirales/economía , Antirretrovirales/uso terapéutico , Política de Salud , Síndrome de Inmunodeficiencia Adquirida/prevención & control , Brasil , Atención a la Salud/economía , Atención a la Salud/normas , Accesibilidad a los Servicios de Salud , Humanos , Investigación/economía , Investigación/legislación & jurisprudencia
16.
Int J Mol Sci ; 21(1)2019 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-31905652

RESUMEN

The microbiome is able to modulate immune responses, alter the physiology of the human organism, and increase the risk of viral infections and development of diseases such as cancer. In this review, we address changes in the cervical microbiota as potential biomarkers to identify the risk of cervical intraepithelial neoplasia (CIN) development and invasive cervical cancer in the context of human papillomavirus (HPV) infection. Current approaches for clinical diagnostics and the manipulation of microbiota with the use of probiotics and through microbiota transplantation are also discussed.


Asunto(s)
Microbiota , Displasia del Cuello del Útero/microbiología , Neoplasias del Cuello Uterino/microbiología , Biomarcadores de Tumor/análisis , Femenino , Genitales Femeninos/microbiología , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/etiología , Displasia del Cuello del Útero/diagnóstico , Displasia del Cuello del Útero/etiología
17.
Retrovirology ; 15(1): 19, 2018 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-29402305

RESUMEN

BACKGROUND: Simian immunodeficiency viruses (SIVs) of chimpanzees and gorillas from Central Africa crossed the species barrier at least four times giving rise to human immunodeficiency virus type 1 (HIV-1) groups M, N, O and P. The paradigm of non-pathogenic lentiviral infections has been challenged by observations of naturally infected chimpanzees with SIVcpz associated with a negative impact on their life span and reproduction, CD4+ T-lymphocyte loss and lymphoid tissue destruction. With the advent and dissemination of new generation sequencing technologies, novel promising markers of immune deficiency have been explored in human and nonhuman primate species, showing changes in the microbiome (dysbiosis) that might be associated with pathogenic conditions. The aim of the present study was to identify and compare enteric viromes of SIVgor-infected and uninfected gorillas using noninvasive sampling and ultradeep sequencing, and to assess the association of virome composition with potential SIVgor pathogenesis in their natural hosts. RESULTS: We analyzed both RNA and DNA virus libraries of 23 fecal samples from 11 SIVgor-infected (two samples from one animal) and 11 uninfected western lowland gorillas from Campo-Ma'an National Park (CP), in southwestern Cameroon. Three bacteriophage families (Siphoviridae, Myoviridae and Podoviridae) represented 67.5 and 68% of the total annotated reads in SIVgor-infected and uninfected individuals, respectively. Conversely, mammalian viral families, such as Herpesviridae and Reoviridae, previously associated with gut- and several mammalian diseases were significantly more abundant (p < 0.003) in the SIVgor-infected group. In the present study, we analyzed, for the first time, the enteric virome of gorillas and their association with SIVgor status. This also provided the first evidence of association of specific mammalian viral families and SIVgor in a putative dysbiosis context. CONCLUSIONS: Our results suggested that viromes might be potentially used as markers of lentiviral disease progression in wild gorilla populations. The diverse mammalian viral families, herein described in SIVgor-infected gorillas, may play a pivotal role in a disease progression still unclear in these animals but already well characterized in pathogenic lentiviral infections in other organisms. Larger sample sets should be further explored to reduce intrinsic sampling variation.


Asunto(s)
Disbiosis/virología , Microbioma Gastrointestinal , Gorilla gorilla/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/virología , Virus/clasificación , Animales , Animales Salvajes , Anticuerpos Antivirales/sangre , Antígenos Virales , Biodiversidad , Análisis por Conglomerados , Disbiosis/etiología , Heces/virología , Síndrome de Inmunodeficiencia Adquirida del Simio/complicaciones , Virus de la Inmunodeficiencia de los Simios/patogenicidad , Carga Viral , Virus/genética
18.
J Immunol ; 194(12): 5968-79, 2015 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-25948815

RESUMEN

Among nonhuman primates, SIV-infected Asian pigtailed macaques (PM) are relatively more susceptible to infection and disease progression than SIV-infected rhesus macaques (RM). In addition, SIV-infected African natural hosts such as the sooty mangabeys (SM) are resistant to disease. The mechanisms associated with such species-related variable clinical outcomes remain ill-defined but hold the potential to provide insights into the underlying mechanisms surrounding HIV pathogenesis. Recent findings indicate that the expression of the heterodimeric gut homing integrin α4ß7 can influence both susceptibility and disease progression in RM. It was reasoned that differences in the frequencies/surface densities of α4ß7-expressing lymphocytes might contribute to the differences in the clinical outcome of SIV infection among NHPs. In this article, we report that CD4(+) T cells from PM constitutively express significantly higher levels of α4ß7 than RM or SM. Retinoic acid, a key regulator of α4ß7 expression, was paradoxically found at higher levels in the plasma of SM versus RM or PM. We also observed pairing of ß7 with αE (αEß7) on CD4(+) T cells in the peripheral blood of SM, but not PM or RM. Finally, the differential mean density of expression of α4ß7 in RM versus SM versus PM was predominantly dictated by species-specific sequence differences at the level of the ß7 promoters, as determined by in vitro reporter/promoter construct transfection studies. We propose that differences in the regulation and expression of α4ß7 may explain, in part, the differences in susceptibility and SIV disease progression in these NHP models.


Asunto(s)
Expresión Génica , Integrinas/genética , Especificidad de la Especie , Animales , Sitios de Unión , Células Sanguíneas/metabolismo , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Cercocebus atys , Clonación Molecular , Genes Reporteros , Inmunofenotipificación , Integrinas/clasificación , Integrinas/metabolismo , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Macaca , Datos de Secuencia Molecular , Filogenia , Primates , Regiones Promotoras Genéticas , Unión Proteica , Receptores CCR5/genética , Análisis de Secuencia de ADN , Síndrome de Inmunodeficiencia Adquirida del Simio/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunología , Factores de Transcripción/metabolismo , Factor de Crecimiento Transformador beta1/sangre , Tretinoina/sangre , Tretinoina/metabolismo
19.
Mem Inst Oswaldo Cruz ; 112(10): 728-731, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28954002

RESUMEN

The classification of human papillomavirus (HPV) intratypic lineages by complete genome sequencing is a determinant in understanding biological differences in association with this disease. In this work, we have characterised complete HPV genomes from southern Brazil. Fifteen cervicovaginal Pap smear negative samples previously categorised as HPV-positive were sequenced using ultradeep sequencing, and 18 complete genomes from 13 different HPV types were assembled. Phylogenetic and genetic distance analyses were performed to classify the HPV genomes into lineages and sublineages. This is the first report describing the distribution of HPV intratype lineages of high and low oncogenic risk in asymptomatic women from southern Brazil.


Asunto(s)
Genoma Viral , Papillomaviridae/genética , Infecciones por Papillomavirus/virología , Enfermedades del Cuello del Útero/virología , Adulto , Brasil , ADN Viral , Femenino , Humanos , Papillomaviridae/aislamiento & purificación , Filogenia , Factores de Riesgo , Frotis Vaginal
20.
Mem Inst Oswaldo Cruz ; 112(7): 492-498, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28591310

RESUMEN

BACKGROUND: Increasing evidence suggests that human papillomavirus (HPV) intratype variants (specific lineages and sublineages) are associated with pathogenesis and progression from HPV infection to persistence and the development of cervical cancer. OBJECTIVES: This study aimed to verify the prevalence of HPV infection and distribution of HPV types and HPV16 variants in southern Brazil in women with normal cytology or intraepithelial lesions. METHODS: HPV typing was determined by L1 gene sequencing. To identify HPV16 variants, the LCR and E6 regions were sequenced, and characteristic single nucleotide variants were identified. FINDINGS: A total of 445 samples were studied, with 355 from cervical scrapes and 90 from cervical biopsies. HPV was detected in 24% and 91% of these samples, respectively. The most prevalent HPV types observed were 16 (cervical, 24%; biopsies, 57%) and 58 (cervical, 12%; biopsies, 12%). Seventy-five percent of the HPV16-positive samples were classified into lineages, with 88% defined as lineage A, 10% as lineage D, and 2% as lineage B. MAIN CONCLUSIONS: This study identified a high frequency of European and North American HPV16 lineages, consistent with the genetic background of the human population in southern Brazil.


Asunto(s)
Variación Genética/genética , Papillomavirus Humano 16/genética , Infecciones por Papillomavirus/virología , Displasia del Cuello del Útero/virología , Neoplasias del Cuello Uterino/virología , Adulto , Brasil , Estudios Transversales , ADN Viral/genética , Femenino , Humanos , Reacción en Cadena de la Polimerasa , Factores Socioeconómicos
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