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1.
Emerg Infect Dis ; 30(5): 1017-1021, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38666645

RESUMO

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.


Assuntos
Estações do Ano , Zoonoses , Humanos , África/epidemiologia , Animais , Zoonoses/epidemiologia , História do Século XXI , História do Século XX
2.
Lancet Reg Health Am ; 21: 100492, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37139265

RESUMO

Background: Adult T-cell leukemia/lymphoma (ATL), one of the most aggressive cancers in the world, occurs in 5% of the 10 million people living with HTLV-1 worldwide. French Guiana, a French overseas territory in South America, is one of the highest endemic areas of HTLV-1 worldwide. Here, we describe the demographic and clinical characteristics and outcome of ATL in this area. Methods: We retrospectively collected data from all patients diagnosed between 2009 and 2019. Patients were distributed according to Shimoyama's classification. Prognostic factors were explored through univariate analysis. Findings: Over the 10-year study period, 41 patients with a median age of 54 years at diagnosis were identified, among whom 56% were women. Sixteen (39%) patients were Maroons, a cultural group descendant of the runaway enslaved Africans from former Dutch Guiana. Among the study population, 23 (56%) had an acute type, 14 (34%) a lymphoma type, and one and one chronic and primary cutaneous tumour, respectively. First-lines of treatment included either chemotherapy or Zidovudine combined with pegylated interferon alpha. The 4-year overall survival was 11.4% for the entire population with 0% and 11% for lymphoma and acute forms, respectively. The median progression-free survival was 93 and 115 days for the acute and lymphoma groups (p = 0.37), respectively. Among the twenty-nine patients who died, 8 (28%) died of toxicity, 7 (24%) died of disease progression and the cause of death remained unknown in 14 (48%) patients. Due to the overall poor prognosis, no significant prognostic factors could be identified. Interpretation: This study provides real-life data from ATL patients in French Guiana, a remote territory in a middle-income region. Patients, mostly Maroons, presented with a younger age and the prognosis was worse than expected compared to Japanese patients. Funding: None.

3.
PLoS Pathog ; 19(4): e1011339, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37093892

RESUMO

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/.


Assuntos
Hominidae , Vírus Espumoso dos Símios , Animais , Humanos , Vírus Espumoso dos Símios/genética , Retroviridae , Anticorpos Neutralizantes , Epitopos de Linfócito B/genética , Anticorpos Anti-HIV
4.
Vaccine ; 41(20): 3171-3177, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37088603

RESUMO

The widespread outbreak of the monkeypox virus (MPXV) recognized in 2022 poses new challenges for public healthcare systems worldwide. With more than 86,000 people infected, there is concern that MPXV may become endemic outside of its original geographical area leading to repeated human spillover infections or continue to be spread person-to-person. Fortunately, classical public health measures (e.g., isolation, contact tracing and quarantine) and vaccination have blunted the spread of the virus, but cases are continuing to be reported in 28 countries in March 2023. We describe here the vaccines and drugs available for the prevention and treatment of MPXV infections. However, although their efficacy against monkeypox (mpox) has been established in animal models, little is known about their efficacy in the current outbreak setting. The continuing opportunity for transmission raises concerns about the potential for evolution of the virus and for expansion beyond the current risk groups. The priorities for action are clear: 1) more data on the efficacy of vaccines and drugs in infected humans must be gathered; 2) global collaborations are necessary to ensure that government authorities work with the private sector in developed and low and middle income countries (LMICs) to provide the availability of treatments and vaccines, especially in historically endemic/enzootic areas; 3) diagnostic and surveillance capacity must be increased to identify areas and populations where the virus is present and may seed resurgence; 4) those at high risk of severe outcomes (e.g., immunocompromised, untreated HIV, pregnant women, and inflammatory skin conditions) must be informed of the risk of infection and be protected from community transmission of MPXV; 5) engagement with the hardest hit communities in a non-stigmatizing way is needed to increase the understanding and acceptance of public health measures; and 6) repositories of monkeypox clinical samples, including blood, fluids, tissues and lesion material must be established for researchers. This MPXV outbreak is a warning that pandemic preparedness plans need additional coordination and resources. We must prepare for continuing transmission, resurgence, and repeated spillovers of MPXV.


Assuntos
Mpox , Vacinas , Gravidez , Animais , Humanos , Feminino , Mpox/epidemiologia , Mpox/prevenção & controle , Monkeypox virus , Vacinação , Surtos de Doenças/prevenção & controle
5.
Nat Commun ; 14(1): 1262, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36878926

RESUMO

The surface envelope glycoprotein (Env) of all retroviruses mediates virus binding to cells and fusion of the viral and cellular membranes. A structure-function relationship for the HIV Env that belongs to the Orthoretrovirus subfamily has been well established. Structural information is however largely missing for the Env of Foamy viruses (FVs), the second retroviral subfamily. In this work we present the X-ray structure of the receptor binding domain (RBD) of a simian FV Env at 2.57 Å resolution, revealing two subdomains and an unprecedented fold. We have generated a model for the organization of the RBDs within the trimeric Env, which indicates that the upper subdomains form a cage-like structure at the apex of the Env, and identified residues K342, R343, R359 and R369 in the lower subdomain as key players for the interaction of the RBD and viral particles with heparan sulfate.


Assuntos
Vírus Espumoso dos Símios , Spumavirus , Retroviridae , Membrana Celular , Glicoproteínas de Membrana
6.
Viruses ; 15(3)2023 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-36992436

RESUMO

Previous human cases or epidemics have suggested that Monkeypox virus (MPXV) can be transmitted through contact with animals of African rainforests. Although MPXV has been identified in many mammal species, most are likely secondary hosts, and the reservoir host has yet to be discovered. In this study, we provide the full list of African mammal genera (and species) in which MPXV was previously detected, and predict the geographic distributions of all species of these genera based on museum specimens and an ecological niche modelling (ENM) method. Then, we reconstruct the ecological niche of MPXV using georeferenced data on animal MPXV sequences and human index cases, and conduct overlap analyses with the ecological niches inferred for 99 mammal species, in order to identify the most probable animal reservoir. Our results show that the MPXV niche covers three African rainforests: the Congo Basin, and Upper and Lower Guinean forests. The four mammal species showing the best niche overlap with MPXV are all arboreal rodents, including three squirrels: Funisciurus anerythrus, Funisciurus pyrropus, Heliosciurus rufobrachium, and Graphiurus lorraineus. We conclude that the most probable MPXV reservoir is F. anerythrus based on two niche overlap metrics, the areas of higher probabilities of occurrence, and available data on MPXV detection.


Assuntos
Monkeypox virus , Mpox , Animais , Humanos , Mpox/diagnóstico , Mamíferos , Sciuridae , Ecossistema
7.
Front Immunol ; 14: 1043600, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36817417

RESUMO

The African continent is considered the largest high endemic area for the oncogenic retrovirus HTLV-1 with an estimated two to five million infected individuals. However, data on epidemiological aspects, in particular prevalence, risk factors and geographical distribution, are still very limited for many regions: on the one hand, few large-scale and representative studies have been performed and, on the other hand, many studies do not include confirmatory tests, resulting in indeterminate serological results, and a likely overestimation of HTLV-1 seroprevalence. For this review, we included the most robust studies published since 1984 on the prevalence of HTLV-1 and the two major diseases associated with this infection in people living in Africa and the Indian Ocean islands: adult T-cell leukemia (ATL) and tropical spastic paraparesis or HTLV-1-associated myelopathy (HAM/TSP). We also considered most of the book chapters and abstracts published at the 20 international conferences on HTLV and related viruses held since 1985, as well as the results of recent meta-analyses regarding the status of HTLV-1 in West and sub-Saharan Africa. Based on this bibliography, it appears that HTLV-1 distribution is very heterogeneous in Africa: The highest prevalences of HTLV-1 are reported in western, central and southern Africa, while eastern and northern Africa show lower prevalences. In highly endemic areas, the HTLV-1 prevalence in the adult population ranges from 0.3 to 3%, increases with age, and is highest among women. In rural areas of Gabon and the Democratic Republic of the Congo (DRC), HTLV-1 prevalence can reach up to 10-25% in elder women. HTLV-1-associated diseases in African patients have rarely been reported in situ on hospital wards, by local physicians. With the exception of the Republic of South Africa, DRC and Senegal, most reports on ATL and HAM/TSP in African patients have been published by European and American clinicians and involve immigrants or medical returnees to Europe (France and the UK) and the United States. There is clearly a huge underreporting of these diseases on the African continent. The genetic diversity of HTLV-1 is greatest in Africa, where six distinct genotypes (a, b, d, e, f, g) have been identified. The most frequent genotype in central Africa is genotype b. The other genotypes found in central Africa (d, e, f and g) are very rare. The vast majority of HTLV-1 strains from West and North Africa belong to genotype a, the so-called 'Cosmopolitan' genotype. These strains form five clades roughly reflecting the geographic origin of the infected individuals. We have recently shown that some of these clades are the result of recombination between a-WA and a-NA strains. Almost all sequences from southern Africa belong to Transcontinental a-genotype subgroup.


Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical , Adulto , Humanos , Feminino , Idoso , Estudos Soroepidemiológicos , Sistemas de Distribuição no Hospital , Variação Genética , África do Sul
8.
N Engl J Med ; 388(7): 671, 2023 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-36791180
9.
Clin Infect Dis ; 76(3): e820-e826, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35903021

RESUMO

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.


Assuntos
Diabetes Mellitus , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Insuficiência Renal Crônica , Adulto , Humanos , Provírus , Infecções por HTLV-I/complicações , Infecções por HTLV-I/epidemiologia , Estudos Transversais , Austrália/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/complicações , Carga Viral , Inquéritos e Questionários , Leucemia de Células T/complicações
10.
J Infect Dis ; 227(6): 752-760, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35867855

RESUMO

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.


Assuntos
Infecção Hospitalar , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Leucemia de Células T , Animais , Humanos , Feminino , Vírus Linfotrópico T Tipo 1 Humano/genética , População Rural , Estudos Transversais , Transmissão Vertical de Doenças Infecciosas , África Central/epidemiologia , Infecções por HTLV-I/epidemiologia
11.
Emerg Infect Dis ; 28(12): 2435-2445, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36328951

RESUMO

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.


Assuntos
Mpox , Criança , Humanos , Adolescente , Mpox/epidemiologia , República Centro-Africana/epidemiologia , Monkeypox virus/genética , Surtos de Doenças , África Central/epidemiologia
12.
N Engl J Med ; 387(19): 1783-1793, 2022 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-36286263
13.
Curr Biol ; 32(21): 4565-4575.e6, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36108636

RESUMO

The Vanuatu archipelago served as a gateway to Remote Oceania during one of the most extensive human migrations to uninhabited lands ∼3,000 years ago. Ancient DNA studies suggest an initial settlement by East Asian-related peoples that was quickly followed by the arrival of Papuan-related populations, leading to a major population turnover. Yet there is uncertainty over the population processes and the sociocultural factors that have shaped the genomic diversity of ni-Vanuatu, who present nowadays among the world's highest linguistic and cultural diversity. Here, we report new genome-wide data for 1,433 contemporary ni-Vanuatu from 29 different islands, including 287 couples. We find that ni-Vanuatu derive their East Asian- and Papuan-related ancestry from the same source populations and descend from relatively synchronous, sex-biased admixture events that occurred ∼1,700-2,300 years ago, indicating a peopling history common to the whole archipelago. However, East Asian-related ancestry proportions differ markedly across islands, suggesting that the Papuan-related population turnover was geographically uneven. Furthermore, we detect Polynesian ancestry arriving ∼600-1,000 years ago to Central and South Vanuatu in both Polynesian-speaking and non-Polynesian-speaking populations. Last, we provide evidence for a tendency of spouses to carry similar genetic ancestry, when accounting for relatedness avoidance. The signal is not driven by strong genetic effects of specific loci or trait-associated variants, suggesting that it results instead from social assortative mating. Altogether, our findings provide an insight into both the genetic history of ni-Vanuatu populations and how sociocultural processes have shaped the diversity of their genomes.


Assuntos
DNA Antigo , Migração Humana , Humanos , Genômica , Genoma Humano , Havaiano Nativo ou Outro Ilhéu do Pacífico , Genética Populacional
14.
Microbiol Spectr ; 10(5): e0298922, 2022 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-36040168

RESUMO

Zika virus (ZIKV) is a mosquito-borne flavivirus that emerged in the Pacific islands in 2007 and spread to the Americas in 2015. The infection remains asymptomatic in most cases but can be associated with severe neurological disorders. Despite massive efforts, no specific drug or vaccine against ZIKV infection is available to date. Claudins are tight-junction proteins that favor the entry of several flaviviruses, including ZIKV. In this study, we identified two peptides derived from the N-terminal sequences of claudin-7 and claudin-1, named CL7.1 and CL1.1, respectively, that inhibited ZIKV infection in a panel of human cell lines. Using cell-to-cell fusion assays, we demonstrated that these peptides blocked the ZIKV E-mediated membrane fusion. A comparison of the antiviral efficacy of CL1.1 and CL7.1 pointed to the importance of the peptide amphipathicity. Electron microscopic analysis revealed that CL1.1 altered the ultrastructure of the viral particles likely by binding the virus lipid envelope. However, amphipathicity could not fully explain the antiviral activity of CL1.1. In silico docking simulations suggested that CL1.1 may also interact with the E protein, near its stem region. Overall, our data suggested that claudin-derived peptides inhibition may be linked to simultaneous interaction with the E protein and the viral lipid envelope. Finally, we found that CL1.1 also blocked infection by yellow fever and Japanese encephalitis viruses but not by HIV-1 or SARS-CoV-2. Our results provide a basis for the future development of therapeutics against a wide range of endemic and emerging flaviviruses. IMPORTANCE Zika virus (ZIKV) is a flavivirus transmitted by mosquito bites that have spread to the Pacific Islands and the Americas over the past decade. The infection remains asymptomatic in most cases but can cause severe neurological disorders. ZIKV is a major public health threat in areas of endemicity, and there is currently no specific antiviral drug or vaccine available. We identified two antiviral peptides deriving from the N-terminal sequences of claudin-7 and claudin-1 with the latter being the most effective. These peptides block the envelope-mediated membrane fusion. Our data suggested that the inhibition was likely achieved by simultaneously interacting with the viral lipid envelope and the E protein. The peptides also inhibited other flaviviruses. These results could provide the basis for the development of therapies that might target a wide array of flaviviruses from current epidemics and possibly future emergences.


Assuntos
Claudinas , Fusão de Membrana , Infecção por Zika virus , Zika virus , Humanos , Antivirais/farmacologia , Claudina-1 , Lipídeos , Peptídeos/farmacologia , Infecção por Zika virus/tratamento farmacológico
15.
PLoS One ; 17(7): e0271320, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35867643

RESUMO

INTRODUCTION: Human T-cell lymphotrophic virus type-1 (HTLV-1) and human immunodeficiency virus (HIV-1) co-infection occur in many populations. People living with HIV-1 and infected with HTLV-1 seem more likely to progress rapidly towards AIDS. Both HTLV-1 and HIV-1 are endemic in Gabon (Central Africa). We investigated HTLV-1 and HIV-1 co-infection in the Haut-Ogooué province, and assessed factors that may favor the rapid evolution and progression to AIDS in co-infected patients. METHODS: Plasma samples from HTLV-1 patients were tested using ELISA, and positive samples were then tested by western blot assay (WB). We used the polymerase chain reaction to detect HTLV-1 Tax/Rex genes using DNA extracted from the buffy coat of ELISA-positives samples. RESULTS: We recruited 299 individuals (mean age 46 years) including 90 (30%) men and 209 (70%) women, all of whom are under treatment at the Ambulatory Treatment Centre of the province. Of these, 45 were ELISA HTLV-1/2 seropositive. According to WB criteria, 21 of 45 were confirmed positive: 20 were HTLV-1 (44%), 1 was HTLV-1/2 (2%), 2 were indeterminate (4%) and 22 were seronegative (49%). PCR results showed that 23 individuals were positive for the Tax/Rex region. Considering both serological and molecular assays, the prevalence of HTLV-1 infection was estimated at 7.7%. Being a woman and increasing age were found to be independent risk factors for co-infection. Mean CD4+ cell counts were higher in HTLV-1/HIV-1 co-infected (578.1 (± 340.8) cells/mm3) than in HIV-1 mono-infected (481.0 (± 299.0) cells/mm3) Individuals. Similarly, the mean HIV-1 viral load was Log 3.0 (± 1.6) copies/ml in mono-infected and Log 2.3 (± 0.7) copies/ml in coinfected individuals. CONCLUSION: We described an overall high prevalence of HTLV-1/HIV-1 co-infection in Gabon. Our findings stress the need of strategies to prevent and manage these co-infections.


Assuntos
Síndrome da Imunodeficiência Adquirida , Coinfecção , Infecções por HIV , Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Western Blotting , Coinfecção/epidemiologia , Feminino , Gabão/epidemiologia , HIV , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HTLV-I/complicações , Infecções por HTLV-I/epidemiologia , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 2 Humano/genética , Humanos , Masculino , Pessoa de Meia-Idade
16.
Sci Rep ; 12(1): 10768, 2022 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-35750759

RESUMO

Monkeypox is an emerging and neglected zoonotic disease whose number of reported cases has been gradually increasing in Central Africa since 1980. This disease is caused by the monkeypox virus (MPXV), which belongs to the genus Orthopoxvirus in the family Poxviridae. Obtaining molecular data is particularly useful for establishing the relationships between the viral strains involved in outbreaks in countries affected by this disease. In this study, we evaluated the use of the MinION real-time sequencer as well as different polishing tools on MinION-sequenced genome for sequencing the MPXV genome originating from a pustular lesion in the context of an epidemic in a remote area of the Central African Republic. The reads corresponding to the MPXV genome were identified using two taxonomic classifiers, Kraken2 and Kaiju. Assembly of these reads led to a complete sequence of 196,956 bases, which is 6322 bases longer than the sequence previously obtained with Illumina sequencing from the same sample. The comparison of the two sequences showed mainly indels at the homopolymeric regions. However, the combined use of Canu with specific polishing tools such as Medaka and Homopolish was the best combination that reduced their numbers without adding mismatches. Although MinION sequencing is known to introduce a number of characteristic errors compared to Illumina sequencing, the new polishing tools allow a better-quality MinION-sequenced genome, thus to be used to help determine strain origin through phylogenetic analysis.


Assuntos
Mpox , Sequenciamento por Nanoporos , República Centro-Africana , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mpox/epidemiologia , Monkeypox virus/genética , Filogenia
17.
Viruses ; 14(5)2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35632593

RESUMO

Zika virus (ZIKV) is a mosquito-borne RNA virus belonging to the Flavivirus genus of the Flaviviridae family. During the 60 years following its discovery in 1947, ZIKV caused little concern for public health as the associated infection was reported as mostly asymptomatic or inducing mild symptoms. However, since 2013, severe neurological symptoms have been associated with ZIKV infection, compelling the World Health Organization to declare a Public Health Emergency of International Concern. Among those symptoms, neurological birth defects may affect children born to mothers infected during pregnancy. Additionally, during the past 8 years, ZIKV transmission through breastfeeding has repeatedly been suggested in epidemiological studies and demonstrated on a mouse model by our team. To better understand the biological factors controlling ZIKV transmission through breastfeeding, we investigated the nature of the viral entities excreted in the breast milk of infected dams and evaluated viral transmission to breastfed pups. We show that both cell-free and cell-associated virus is excreted into breast milk and that ZIKV is efficiently transmitted to the breastfed pups. Additionally, we studied murine breast milk cell types, and identified a majority of mammary luminal cells. Finally, we investigated the effect on ZIKV infectivity of several breast milk components that are antiviral against different viruses such as lactoferrin (LF) and lactalbumin (LA), or free fatty acids (FFA). We showed no effect of LF and LA, whereas FFA inactivated the virus. These results bring new insight concerning the mechanisms of ZIKV transmission during breastfeeding and identify biological factors modulating it. These elements should be considered in risk assessment of ZIKV mother-to-child transmission.


Assuntos
Infecção por Zika virus , Zika virus , Animais , Antivirais/farmacologia , Fatores Biológicos/farmacologia , Feminino , Humanos , Transmissão Vertical de Doenças Infecciosas , Camundongos , Leite Humano , Gravidez , Vírus Satélites , Zika virus/genética
18.
PLoS Pathog ; 18(5): e1010470, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35605011

RESUMO

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/.


Assuntos
Hominidae , Infecções por Retroviridae , Vírus Espumoso dos Símios , Spumavirus , Animais , Vírus de DNA , Gorilla gorilla , Humanos
19.
BMC Res Notes ; 15(1): 87, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241131

RESUMO

OBJECTIVE: A single study conducted about three decades ago on hepatitis D virus (HDV) infection among Baka pygmies in Cameroon reported a very high anti-HDV antibodies prevalence of 46%, but HDV genetic diversity has not been studied in this population. The genetic diversity of strains from endemic ancient populations may help to understand the origin and evolutionary history of viruses. This study aimed to investigate the HDV seroprevalence and the genetic diversity in three remote Cameroonian Pygmies with chronic HBV infection. RESULTS: An unusually high 69% (36/52) level of HDV infection was found among HBsAg-positive pygmies in Cameroon. HDV RNA was detected and sequenced in 38.8% (14/36). The phylogenetic analysis revealed that 9/14 strains (64.3%) were identified and classified as genotype 1 (HDV-1) and 5/14 (35.6%) as genotype 7 (HDV-7), respectively with a bootstrap value of 100%. The further analysis showed the co-circulation of highly diverse HDV genotypes HDV-1 and HDV-7 in this population. These results highlight the endemicity of HDV infection in Central Africa. The highly diverse HDV-1 and HDV-7 in pygmies suggest an African origin of HDV. However, further studies are needed with larger sample size.


Assuntos
Variação Genética , Vírus Delta da Hepatite , Camarões/epidemiologia , Genótipo , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Vírus Delta da Hepatite/genética , Filogenia , Prevalência , Estudos Soroepidemiológicos
20.
Clin Microbiol Rev ; 35(2): e0007821, 2022 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-35195446

RESUMO

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.


Assuntos
Infecções por HTLV-I , Vírus Linfotrópico T Tipo 1 Humano , Leucemia-Linfoma de Células T do Adulto , Paraparesia Espástica Tropical , Adulto , Infecções por HTLV-I/diagnóstico , Infecções por HTLV-I/epidemiologia , Infecções por HTLV-I/prevenção & controle , Humanos , Leucemia-Linfoma de Células T do Adulto/epidemiologia , Paraparesia Espástica Tropical/epidemiologia , Paraparesia Espástica Tropical/patologia , Saúde Pública
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