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1.
Nature ; 592(7855): 583-589, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33854233

RESUMEN

The Pacific region is of major importance for addressing questions regarding human dispersals, interactions with archaic hominins and natural selection processes1. However, the demographic and adaptive history of Oceanian populations remains largely uncharacterized. Here we report high-coverage genomes of 317 individuals from 20 populations from the Pacific region. We find that the ancestors of Papuan-related ('Near Oceanian') groups underwent a strong bottleneck before the settlement of the region, and separated around 20,000-40,000 years ago. We infer that the East Asian ancestors of Pacific populations may have diverged from Taiwanese Indigenous peoples before the Neolithic expansion, which is thought to have started from Taiwan around 5,000 years ago2-4. Additionally, this dispersal was not followed by an immediate, single admixture event with Near Oceanian populations, but involved recurrent episodes of genetic interactions. Our analyses reveal marked differences in the proportion and nature of Denisovan heritage among Pacific groups, suggesting that independent interbreeding with highly structured archaic populations occurred. Furthermore, whereas introgression of Neanderthal genetic information facilitated the adaptation of modern humans related to multiple phenotypes (for example, metabolism, pigmentation and neuronal development), Denisovan introgression was primarily beneficial for immune-related functions. Finally, we report evidence of selective sweeps and polygenic adaptation associated with pathogen exposure and lipid metabolism in the Pacific region, increasing our understanding of the mechanisms of biological adaptation to island environments.


Asunto(s)
Adaptación Biológica/genética , Evolución Biológica , Genética de Población , Genoma Humano/genética , Genómica , Migración Humana/historia , Islas , Nativos de Hawái y Otras Islas del Pacífico/genética , Animales , Australia , Conjuntos de Datos como Asunto , Asia Oriental , Introgresión Genética , Historia Antigua , Humanos , Hombre de Neandertal/genética , Oceanía , Océano Pacífico , Taiwán
2.
PLoS Pathog ; 19(4): e1011339, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-37093892

RESUMEN

Infection with viruses of animal origin pose a significant threat to human populations. Simian foamy viruses (SFVs) are frequently transmitted to humans, in which they establish a life-long infection, with the persistence of replication-competent virus. However, zoonotic SFVs do not induce severe disease nor are they transmitted between humans. Thus, SFVs represent a model of zoonotic retroviruses that lead to a chronic infection successfully controlled by the human immune system. We previously showed that infected humans develop potent neutralizing antibodies (nAbs). Within the viral envelope (Env), the surface protein (SU) carries a variable region that defines two genotypes, overlaps with the receptor binding domain (RBD), and is the exclusive target of nAbs. However, its antigenic determinants are not understood. Here, we characterized nAbs present in plasma samples from SFV-infected individuals living in Central Africa. Neutralization assays were carried out in the presence of recombinant SU that compete with SU at the surface of viral vector particles. We defined the regions targeted by the nAbs using mutant SU proteins modified at the glycosylation sites, RBD functional subregions, and genotype-specific sequences that present properties of B-cell epitopes. We observed that nAbs target conformational epitopes. We identified three major epitopic regions: the loops at the apex of the RBD, which likely mediate interactions between Env protomers to form Env trimers, a loop located in the vicinity of the heparan binding site, and a region proximal to the highly conserved glycosylation site N8. We provide information on how nAbs specific for each of the two viral genotypes target different epitopes. Two common immune escape mechanisms, sequence variation and glycan shielding, were not observed. We propose a model according to which the neutralization mechanisms rely on the nAbs to block the Env conformational change and/or interfere with binding to susceptible cells. As the SFV RBD is structurally different from known retroviral RBDs, our data provide fundamental knowledge on the structural basis for the inhibition of viruses by nAbs. Trial registration: The study was registered at www.clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT03225794/.


Asunto(s)
Hominidae , Virus Espumoso de los Simios , Animales , Humanos , Virus Espumoso de los Simios/genética , Retroviridae , Anticuerpos Neutralizantes , Epítopos de Linfocito B/genética , Anticuerpos Anti-VIH
3.
J Infect Dis ; 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39126336

RESUMEN

BACKGROUND: Ebola (EBOV) and Sudan (SUDV) orthoebolaviruses are responsible for lethal haemorrhagic fever outbreaks in humans in Central and West Africa, and in apes that can be at the source of human outbreaks for EBOV. METHODS: To assess the risk of exposure to orthoebolaviruses through contact with non-human primates (NHP), we tested the presence of antibodies against different viral proteins with a microsphere-based multiplex immunoassay in a case-control study on bites from NHPs in forest areas from Cameroon (n=795), and in cross-sectional surveys from other rural populations (n=622) of the same country. RESULTS: Seroreactivities against at least two viral proteins were detected in 13% and 12% of the samples for EBOV and SUDV, respectively. Probability of seroreactivity was not associated with history of NHP bites, but was three times higher in Pygmies compared to Bantus. Although no neutralizing antibodies to EBOV and SUDV were detected in a selected series of highly reactive samples, avidity results indicate strong affinity to SUDV antigens. CONCLUSION: The detection of high level of seroreactivities against orthoebolaviruses in rural Cameroon where no outbreaks have been reported, raises the possibilities of silent circulation of orthoebolavirus, or of other not yet documented filoviruses, in these forested regions.

4.
Emerg Infect Dis ; 30(5): 1017-1021, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38666645

RESUMEN

Across 133 confirmed mpox zoonotic index cases reported during 1970-2021 in Africa, cases occurred year-round near the equator, where climate is consistent. However, in tropical regions of the northern hemisphere under a dry/wet season cycle, cases occurred seasonally. Our findings further support the seasonality of mpox zoonotic transmission risk.


Asunto(s)
Estaciones del Año , Zoonosis , Humanos , África/epidemiología , Animales , Zoonosis/epidemiología , Historia del Siglo XXI , Historia del Siglo XX
5.
PLoS Pathog ; 18(5): e1010470, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35605011

RESUMEN

Zoonotic simian foamy viruses (SFV) establish lifelong infection in their human hosts. Despite repeated transmission of SFV from nonhuman primates to humans, neither transmission between human hosts nor severe clinical manifestations have been reported. We aim to study the immune responses elicited by chronic infection with this retrovirus and previously reported that SFV-infected individuals generate potent neutralizing antibodies that block cell infection by viral particles. Here, we assessed whether human plasma antibodies block SFV cell-to-cell transmission and present the first description of cell-to-cell spreading of zoonotic gorilla SFV. We set-up a microtitration assay to quantify the ability of plasma samples from 20 Central African individuals infected with gorilla SFV and 9 uninfected controls to block cell-associated transmission of zoonotic gorilla SFV strains. We used flow-based cell cytometry and fluorescence microscopy to study envelope protein (Env) localization and the capacity of plasma antibodies to bind to infected cells. We visualized the cell-to-cell spread of SFV by real-time live imaging of a GFP-expressing prototype foamy virus (CI-PFV) strain. None of the samples neutralized cell-associated SFV infection, despite the inhibition of cell-free virus. We detected gorilla SFV Env in the perinuclear region, cytoplasmic vesicles and at the cell surface. We found that plasma antibodies bind to Env located at the surface of cells infected with primary gorilla SFV strains. Extracellular labeling of SFV proteins by human plasma samples showed patchy staining at the base of the cell and dense continuous staining at the cell apex, as well as staining in the intercellular connections that formed when previously connected cells separated from each other. In conclusion, SFV-specific antibodies from infected humans do not block cell-to-cell transmission, at least in vitro, despite their capacity to bind to the surface of infected cells. Trial registration: Clinical trial registration: www.clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03225794/.


Asunto(s)
Hominidae , Infecciones por Retroviridae , Virus Espumoso de los Simios , Spumavirus , Animales , Virus ADN , Gorilla gorilla , Humanos
6.
Clin Microbiol Rev ; 35(2): e0007821, 2022 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-35195446

RESUMEN

Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The burden of HTLV-1 infection appears to be geographically concentrated, with high prevalence in discrete regions and populations. While most high-income countries have introduced HTLV-1 screening of blood donations, few other public health measures have been implemented to prevent infection or its consequences. Recent advocacy from concerned researchers, clinicians, and community members has emphasized the potential for improved prevention and management of HTLV-1 infection. Despite all that has been learned in the 4 decades following the discovery of HTLV-1, gaps in knowledge across clinical and public health aspects persist, impeding optimal control and prevention, as well as the development of policies and guidelines. Awareness of HTLV-1 among health care providers, communities, and affected individuals remains limited, even in countries of endemicity. This review provides a comprehensive overview on HTLV-1 epidemiology and on clinical and public health and highlights key areas for further research and collaboration to advance the health of people with and at risk of HTLV-1 infection.


Asunto(s)
Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T del Adulto , Paraparesia Espástica Tropical , Adulto , Infecciones por HTLV-I/diagnóstico , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-I/prevención & control , Humanos , Leucemia-Linfoma de Células T del Adulto/epidemiología , Paraparesia Espástica Tropical/epidemiología , Paraparesia Espástica Tropical/patología , Salud Pública
7.
J Infect Dis ; 227(6): 752-760, 2023 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-35867855

RESUMEN

BACKGROUND: Central Africa is one of the largest areas of high endemicity for human T-cell leukemia virus-1 (HTLV-1). However, no preventive measures are yet implemented to reduce its transmission, which can be sexual, from mother-to-child, or through contaminated blood products. Rare zoonotic transmissions from nonhuman primates (NHPs) have also been reported in this region. Here we investigated the HTLV-1 prevalence and associated risk factors in a rural population in Cameroon. METHODS: From 2019 to 2021, we performed a cross-sectional survey in the eastern region of Cameroon. HTLV-1 infection was first screened by ELISA, then tested by western blot and envelope gene targeted polymerase chain reaction. Risk factors associated with HTLV-1 infection were identified by logistic regression in univariable and multivariable analyses. RESULTS: Among 3400 participants, HTLV-1 prevalence was 1.1% (95% confidence interval [CI], .7-1.5). Factors independently associated with HTLV-1 infection were Pygmy ethnicity (adjusted odd ratio [aOR], 2.9; 95% CI, 1.3-6.2), history of surgery (aOR, 6.3; 95% CI, 2.2-17.8), and NHP bite (aOR, 6.6; 95% CI, 2.2-19.8). CONCLUSIONS: These results suggest both iatrogenic and zoonotic transmission of HTLV-1 in Cameroon. Further studies are needed to assess the risk of nosocomial transmission of HTLV-1, to guide public health authorities in implementing preventive measures to control HTLV-1 transmission.


Asunto(s)
Infección Hospitalaria , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Animales , Humanos , Femenino , Virus Linfotrópico T Tipo 1 Humano/genética , Población Rural , Estudios Transversales , Transmisión Vertical de Enfermedad Infecciosa , África Central/epidemiología , Infecciones por HTLV-I/epidemiología
8.
Clin Infect Dis ; 76(3): e820-e826, 2023 02 08.
Artículo en Inglés | MEDLINE | ID: mdl-35903021

RESUMEN

BACKGROUND: A link between chronic inflammation and several noncommunicable diseases (NCDs) has been established. Although chronic infection with the human T-cell leukemia virus type 1 (HTLV-1) is the recognized cause of several inflammatory diseases and these are associated with a high number of HTLV-1-infected cells in peripheral blood (proviral load [PVL]), possible interactions between PVL and NCDs have not been studied at a community level. METHODS: Adult Aboriginal residents of 7 remote communities were invited to complete a health survey between 25 August 2014 and 30 June 2018. Blood was drawn for HTLV-1 serology and PVL, and relevant medical conditions were obtained from health records. Associations between HTLV-1 PVL and diabetes, chronic kidney disease (CKD), and coronary artery disease (CAD) were determined using logistic regression, adjusting for available confounders. RESULTS: Among 510 participants (56% of the estimated adult resident population, 922), 197 (38.6%) were HTLV-1-infected. A high HTLV-1 PVL was associated with a 2-fold increase in the odds of diabetes and CKD (diabetes, adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.06-3.61; P = .033 and CKD: aOR, 2.00; 95% CI, 1.03-3.8; P = .041). A nonsignificant association between high PVL and CAD (aOR, 7.08; 95% CI, 1.00-50.18; P = .05) was found for participants aged <50 years at the time of angiography. CONCLUSIONS: In a community-based study in central Australia, people with HTLV-1 who had high HTLV-1 PVL were more likely to have diabetes and CKD. These findings have potential clinical implications.


Asunto(s)
Diabetes Mellitus , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Insuficiencia Renal Crónica , Adulto , Humanos , Provirus , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/epidemiología , Estudios Transversales , Australia/epidemiología , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/complicaciones , Carga Viral , Encuestas y Cuestionarios , Leucemia de Células T/complicaciones
9.
Emerg Infect Dis ; 28(12): 2435-2445, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36328951

RESUMEN

We analyzed monkeypox disease surveillance in Central African Republic (CAR) during 2001-2021. Surveillance data show 95 suspected outbreaks, 40 of which were confirmed as monkeypox, comprising 99 confirmed and 61 suspected monkeypox cases. After 2018, CAR's annual rate of confirmed outbreaks increased, and 65% of outbreaks occurred in 2 forested regions bordering the Democratic Republic of the Congo. The median patient age for confirmed cases was 15.5 years. The overall case-fatality ratio was 7.5% (12/160) for confirmed and suspected cases, 9.6% (8/83) for children <16 years of age. Decreasing cross-protective immunity from smallpox vaccination and recent ecologic alterations likely contribute to increased monkeypox outbreaks in Central Africa. High fatality rates associated with monkeypox virus clade I also are a local and international concern. Ongoing investigations of zoonotic sources and environmental changes that increase human exposure could inform practices to prevent monkeypox expansion into local communities and beyond endemic areas.


Asunto(s)
Mpox , Niño , Humanos , Adolescente , Mpox/epidemiología , República Centroafricana/epidemiología , Monkeypox virus/genética , Brotes de Enfermedades , África Central/epidemiología
10.
Clin Infect Dis ; 73(7): e1498-e1506, 2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-32936911

RESUMEN

BACKGROUND: The human T-cell leukemia virus type 1 (HTLV-1) subtype c is endemic to central Australia. We report the first large-scale, community-based, health survey of HTLV-1 and its disease associations in this setting. METHODS: Aboriginal community residents aged >2 years in 7 remote communities were invited to do a health survey that included a questionnaire, spirometry, and clinical examination by a physician blinded to HTLV-1 status, clinical records, and spirometry results. Blood was drawn for HTLV-1 serology and proviral load (PVL). Pulmonary disease was assessed clinically and spirometrically and, where records were available, radiologically after the clinical assessment. Associations between specific diseases and HTLV-1 status were determined using logistic regression, adjusting for available confounders. RESULTS: Overall, 579 residents (164 children aged 3-17 years; 415 adults) were examined (37.7% of the estimated resident population). HTLV-1 prevalences for children and adults were 6.1% and 39.3%, respectively. No associations were found between HTLV-1 and any assessed clinical condition among children. Chronic pulmonary disease and gait abnormalities were more common among adults with HTLV-1 infection. Adjusted odds ratios among participants with PVL ≥1000 per 105 peripheral blood leukocytes were 7.08 (95% confidence interval [CI], 2.67-18.74; P < .001), 9.81 (95% CI, 3.52-27.35; P < .001), and 14.4 (95% CI, 4.99-41.69; P < .001) for clinically defined chronic pulmonary disease, moderate-severe expiratory airflow limitation, and radiologically determined bronchiectasis/bronchiolitis, respectively, and 5.21 (95% CI, 1.50-18.07; P = .009) for gait abnormalities. CONCLUSIONS: In the first study of HTLV-1 disease associations based on community recruitment and blinded assessment, HTLV-1 infection was strongly associated with pulmonary disease and gait abnormalities.


Asunto(s)
Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Enfermedades Pulmonares , Estudios Transversales , Infecciones por HTLV-I/complicaciones , Infecciones por HTLV-I/epidemiología , Humanos , Carga Viral
11.
Mol Cancer ; 20(1): 86, 2021 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-34092254

RESUMEN

BACKGROUND: Human T cell Leukemia virus type 1 (HTLV-I) is etiologically linked to adult T cell leukemia/lymphoma (ATL) and an inflammatory neurodegenerative disease called HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP). The exact genetic or epigenetic events and/or environmental factors that influence the development of ATL, or HAM/TSP diseases are largely unknown. The tumor suppressor gene, Fragile Histidine Triad Diadenosine Triphosphatase (FHIT), is frequently lost in cancer through epigenetic modifications and/or deletion. FHIT is a tumor suppressor acting as genome caretaker by regulating cellular DNA repair. Indeed, FHIT loss leads to replicative stress and accumulation of double DNA strand breaks. Therefore, loss of FHIT expression plays a key role in cellular transformation. METHODS: Here, we studied over 400 samples from HTLV-I-infected individuals with ATL, TSP/HAM, or asymptomatic carriers (AC) for FHIT loss and expression. We examined the epigenetic status of FHIT through methylation specific PCR and bisulfite sequencing; and correlated these results to FHIT expression in patient samples. RESULTS: We found that epigenetic alteration of FHIT is specifically found in chronic and acute ATL but is absent in asymptomatic HTLV-I carriers and TSP/HAM patients' samples. Furthermore, the extent of FHIT methylation in ATL patients was quantitatively comparable in virus-infected and virus non-infected cells. We also found that longitudinal HTLV-I carriers that progressed to smoldering ATL and descendants of ATL patients harbor FHIT methylation. CONCLUSIONS: These results suggest that germinal epigenetic mutation of FHIT represents a preexisting mark predisposing to the development of ATL diseases. These findings have important clinical implications as patients with acute ATL are rarely cured. Our study suggests an alternative strategy to the current "wait and see approach" in that early screening of HTLV-I-infected individuals for germinal epimutation of FHIT and early treatment may offer significant clinical benefits.


Asunto(s)
Ácido Anhídrido Hidrolasas/genética , Infecciones por HTLV-I/genética , Leucemia-Linfoma de Células T del Adulto/genética , Proteínas de Neoplasias/genética , Metilación de ADN/genética , Progresión de la Enfermedad , Epigénesis Genética , Humanos , Paraparesia Espástica Tropical/genética , Estudios Retrospectivos
12.
N Engl J Med ; 388(7): 671, 2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36791180
13.
PLoS Pathog ; 15(2): e1007589, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30818370

RESUMEN

Human T Lymphotropic virus (HTLV) infection can persist in individuals resulting, at least in part, from viral escape of the innate immunity, including inhibition of type I interferon response in infected T-cells. Plasmacytoid dendritic cells (pDCs) are known to bypass viral escape by their robust type I interferon production. Here, we demonstrated that pDCs produce type I interferons upon physical cell contact with HTLV-infected cells, yet pDC activation inversely correlates with the ability of the HTLV-producing cells to transmit infection. We show that pDCs sense surface associated-HTLV present with glycan-rich structure referred to as biofilm-like structure, which thus represents a newly described viral structure triggering the antiviral response by pDCs. Consistently, heparan sulfate proteoglycans and especially the cell surface pattern of terminal ß-galactoside glycosylation, modulate the transmission of the immunostimulatory RNA to pDCs. Altogether, our results uncover a function of virus-containing cell surface-associated glycosylated structures in the activation of innate immunity.


Asunto(s)
Células Dendríticas/fisiología , Infecciones por HTLV-I/metabolismo , Citocinas , Galactósidos/metabolismo , Glicosilación , Infecciones por HTLV-I/inmunología , Virus Linfotrópico T Tipo 1 Humano/inmunología , Virus Linfotrópico T Tipo 1 Humano/patogenicidad , Virus Linfotrópico T Tipo 2 Humano/inmunología , Virus Linfotrópico T Tipo 2 Humano/patogenicidad , Humanos , Inmunidad Innata/fisiología , Interferón Tipo I/inmunología , Interferón-alfa/inmunología , Interferón-alfa/metabolismo , Células Jurkat , Linfocitos T/inmunología , Linfocitos T/fisiología
14.
J Infect Dis ; 221(10): 1724-1733, 2020 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-31822908

RESUMEN

BACKGROUND: Zoonotic simian foamy viruses (SFVs) establish persistent infections in humans, for whom the long-term consequences for health are poorly described. In this study, we aimed to characterize blood-cell phenotypes and plasma biomarkers associated with gorilla SFV infection in humans. METHODS: We used a case-control design to compare 15 Cameroonian hunters infected with gorilla SFV (cases) to 15 controls matched for age and ethnicity. A flow cytometry-based phenotypic study and quantification of plasma immune biomarkers were carried out on blood samples from all participants. Wilcoxon signed-rank tests were used to compare cases and controls. RESULTS: Cases had a significantly higher percentage of CD8 T lymphocytes than controls (median, 17.6% vs 13.7%; P = .03) but similar levels of B, natural killer, and CD4 T lymphocytes. Cases also had a lower proportion of recent CD4 thymic emigrants (10.9% vs 18.6%, P = .05), a higher proportion of programmed death receptor 1 (PD-1) expressing memory CD4 T lymphocytes (31.7% vs 24.7%, P = .01), and higher plasma levels of the soluble CD163 scavenger receptor (0.84 vs .59 µg/mL, P = .003) than controls. CONCLUSIONS: We show, for the first time, that chronic infection with SFV is associated with T lymphocyte differentiation and monocyte activation.


Asunto(s)
Linfocitos T CD4-Positivos/fisiología , Linfocitos T CD8-positivos/fisiología , Infecciones por Retroviridae/inmunología , Virus Espumoso de los Simios , Zoonosis , Adulto , Anciano , Animales , Estudios de Casos y Controles , Regulación de la Expresión Génica/inmunología , Humanos , Inhibidores de Puntos de Control Inmunológico/metabolismo , Masculino , Persona de Mediana Edad , Primates , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/metabolismo
15.
Am J Hum Genet ; 101(5): 725-736, 2017 Nov 02.
Artículo en Inglés | MEDLINE | ID: mdl-29100086

RESUMEN

The transatlantic slave trade was the largest forced migration in world history. However, the origins of the enslaved Africans and their admixture dynamics remain unclear. To investigate the demographic history of African-descendant Marron populations, we generated genome-wide data (4.3 million markers) from 107 individuals from three African-descendant populations in South America, as well as 124 individuals from six west African populations. Throughout the Americas, thousands of enslaved Africans managed to escape captivity and establish lasting communities, such as the Noir Marron. We find that this population has the highest proportion of African ancestry (∼98%) of any African-descendant population analyzed to date, presumably because of centuries of genetic isolation. By contrast, African-descendant populations in Brazil and Colombia harbor substantially more European and Native American ancestry as a result of their complex admixture histories. Using ancestry tract-length analysis, we detect different dates for the European admixture events in the African-Colombian (1749 CE; confidence interval [CI]: 1737-1764) and African-Brazilian (1796 CE; CI: 1789-1804) populations in our dataset, consistent with the historically attested earlier influx of Africans into Colombia. Furthermore, we find evidence for sex-specific admixture patterns, resulting from predominantly European paternal gene flow. Finally, we detect strong genetic links between the African-descendant populations and specific source populations in Africa on the basis of haplotype sharing patterns. Although the Noir Marron and African-Colombians show stronger affinities with African populations from the Bight of Benin and the Gold Coast, the African-Brazilian population from Rio de Janeiro has greater genetic affinity with Bantu-speaking populations from the Bight of Biafra and west central Africa.


Asunto(s)
Población Negra/genética , África , Brasil , Femenino , Guyana Francesa , Flujo Génico/genética , Genética de Población , Estudio de Asociación del Genoma Completo/métodos , Haplotipos , Hispánicos o Latinos/genética , Humanos , Masculino , Polimorfismo de Nucleótido Simple/genética , Suriname , Población Blanca/genética
16.
N Engl J Med ; 387(19): 1783-1793, 2022 11 10.
Artículo en Inglés | MEDLINE | ID: mdl-36286263
17.
J Virol ; 93(11)2019 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-30894477

RESUMEN

Cross-species transmission of simian foamy viruses (SFVs) from nonhuman primates (NHPs) to humans is currently ongoing. These zoonotic retroviruses establish lifelong persistent infection in their human hosts. SFV are apparently nonpathogenic in vivo, with ubiquitous in vitro tropism. Here, we aimed to identify envelope B-cell epitopes that are recognized following a zoonotic SFV infection. We screened a library of 169 peptides covering the external portion of the envelope from the prototype foamy virus (SFVpsc_huHSRV.13) for recognition by samples from 52 Central African hunters (16 uninfected and 36 infected with chimpanzee, gorilla, or Cercopithecus SFV). We demonstrate the specific recognition of peptide N96-V110 located in the leader peptide, gp18LP Forty-three variant peptides with truncations, alanine substitutions, or amino acid changes found in other SFV species were tested. We mapped the epitope between positions 98 and 108 and defined six amino acids essential for recognition. Most plasma samples from SFV-infected humans cross-reacted with sequences from apes and Old World monkey SFV species. The magnitude of binding to peptide N96-V110 was significantly higher for samples of individuals infected with a chimpanzee or gorilla SFV than those infected with a Cercopithecus SFV. In conclusion, we have been the first to define an immunodominant B-cell epitope recognized by humans following zoonotic SFV infection.IMPORTANCE Foamy viruses are the oldest known retroviruses and have been mostly described to be nonpathogenic in their natural animal hosts. SFVs can be transmitted to humans, in whom they establish persistent infection, like the simian lenti- and deltaviruses that led to the emergence of two major human pathogens, human immunodeficiency virus type 1 and human T-lymphotropic virus type 1. This is the first identification of an SFV-specific B-cell epitope recognized by human plasma samples. The immunodominant epitope lies in gp18LP, probably at the base of the envelope trimers. The NHP species the most genetically related to humans transmitted SFV strains that induced the strongest antibody responses. Importantly, this epitope is well conserved across SFV species that infect African and Asian NHPs.


Asunto(s)
Virus Espumoso de los Simios/inmunología , Proteínas del Envoltorio Viral/inmunología , Zoonosis/inmunología , Adulto , Animales , Anticuerpos Antivirales/sangre , Camerún , Cercopithecus/virología , ADN Viral/sangre , Epítopos de Linfocito B/genética , Epítopos de Linfocito B/inmunología , Gabón , Gorilla gorilla/virología , Hominidae/inmunología , Hominidae/virología , Humanos , Masculino , Persona de Mediana Edad , Pan troglodytes/virología , Infecciones por Retroviridae/virología , Virus Espumoso de los Simios/genética , Spumavirus/genética , Spumavirus/inmunología , Proteínas del Envoltorio Viral/genética , Zoonosis/genética , Zoonosis/virología
18.
PLoS Pathog ; 14(10): e1007293, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30296302

RESUMEN

Human diseases of zoonotic origin are a major public health problem. Simian foamy viruses (SFVs) are complex retroviruses which are currently spilling over to humans. Replication-competent SFVs persist over the lifetime of their human hosts, without spreading to secondary hosts, suggesting the presence of efficient immune control. Accordingly, we aimed to perform an in-depth characterization of neutralizing antibodies raised by humans infected with a zoonotic SFV. We quantified the neutralizing capacity of plasma samples from 58 SFV-infected hunters against primary zoonotic gorilla and chimpanzee SFV strains, and laboratory-adapted chimpanzee SFV. The genotype of the strain infecting each hunter was identified by direct sequencing of the env gene amplified from the buffy coat with genotype-specific primers. Foamy virus vector particles (FVV) enveloped by wild-type and chimeric gorilla SFV were used to map the envelope region targeted by antibodies. Here, we showed high titers of neutralizing antibodies in the plasma of most SFV-infected individuals. Neutralizing antibodies target the dimorphic portion of the envelope protein surface domain. Epitopes recognized by neutralizing antibodies have been conserved during the cospeciation of SFV with their nonhuman primate host. Greater neutralization breadth in plasma samples of SFV-infected humans was statistically associated with smaller SFV-related hematological changes. The neutralization patterns provide evidence for persistent expression of viral proteins and a high prevalence of coinfection. In conclusion, neutralizing antibodies raised against zoonotic SFV target immunodominant and conserved epitopes located in the receptor binding domain. These properties support their potential role in restricting the spread of SFV in the human population.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Vectores de Enfermedades , Epítopos/inmunología , Hominidae/inmunología , Infecciones por Retroviridae/transmisión , Virus Espumoso de los Simios/aislamiento & purificación , Proteínas del Envoltorio Viral/inmunología , Adulto , Secuencia de Aminoácidos , Animales , Anticuerpos Neutralizantes/inmunología , Sitios de Unión , Gorilla gorilla/virología , Hominidae/sangre , Hominidae/virología , Humanos , Masculino , Persona de Mediana Edad , Pan troglodytes/virología , Infecciones por Retroviridae/virología
19.
Transfusion ; 60(7): 1483-1491, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32415686

RESUMEN

BACKGROUND: The African continent is considered to be the largest endemic area of HTLV-1 infection, with at least several million infected individuals. Systematic screening of blood donors can prevent the transmission of HTLV-1 in blood. Gabon is one of the countries with the highest prevalence of HTLV-1 worldwide, and yet the routine testing of blood donors has still not been introduced. METHODS: All blood donations collected between April and July 2017 at the Centre National de Transfusion Sanguine of Gabon were studied. Plasma samples were screened by ELISA for the presence of HTLV-1/2 antibodies. Western blot (WB) and polymerase chain reaction (PCR) tests were used for confirmation. RESULTS: In total, 3123 blood donors were tested, including 1740 repeat and 1378 first-time blood donors (FTBDs). Of them, 132 samples tested positive for HTLV-1/2 by ELISA (4.2%). WB and PCR confirmed HTLV-1 infection for 23 individuals. The overall prevalence of HTLV-1 was 0.74% [95% CI 0.47%-1.10%], 1% in FTBD, and 0.5% in repeat donors. Age and sex-adjusted prevalence was five-fold lower in FTBD than in the general adult population of rural areas of Gabon. All detected HTLV-1 strains belonged to the central African HTLV-1b genotype but were highly diverse. CONCLUSION: We report an overall prevalence of HTLV-1 of 0.74%, one of the highest values reported for blood donors in Africa. Given the high risk of HTLV-1 transmission in blood, it is necessary to conduct cost-effectiveness studies to determine the need and feasibility of implementing screening of HTLV-1 in blood donors in Gabon.


Asunto(s)
Antígenos Virales/sangre , Donantes de Sangre , Genotipo , Infecciones por HTLV-I , Virus Linfotrópico T Tipo 1 Humano , Adolescente , Adulto , Ensayo de Inmunoadsorción Enzimática , Femenino , Gabón , Infecciones por HTLV-I/sangre , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-I/genética , Virus Linfotrópico T Tipo 1 Humano/genética , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Prevalencia
20.
Emerg Infect Dis ; 25(8): 1602-1604, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31216261

RESUMEN

Monkeypox is a rare viral zoonotic disease; primary infections are reported from remote forest areas of Central and West Africa. We report an investigation of a monkeypox outbreak in Lobaye, southwest Central African Republic, in October 2018.


Asunto(s)
Monkeypox virus , Mpox/epidemiología , Mpox/transmisión , Adolescente , Adulto , Animales , República Centroafricana/epidemiología , Niño , Preescolar , Brotes de Enfermedades , Familia , Femenino , Personal de Salud , Historia del Siglo XXI , Humanos , Lactante , Masculino , Mpox/historia , Mpox/virología , Adulto Joven , Zoonosis
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