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1.
Clin Infect Dis ; 73(7): e1445-e1453, 2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-33119064

RESUMEN

BACKGROUND: Hemotropic mycoplasmas, previously classified in the genus Eperythrozoon, have been reported as causing human infections in Brazil, China, Japan, and Spain. METHODS: In 2017, we detected DNA from Candidatus Mycoplasma haemohominis in the blood of a Melanesian patient from New Caledonia presenting with febrile splenomegaly, weight loss, life-threatening autoimmune hemolytic anemia, and hemophagocytosis. The full genome of the bacterium was sequenced from a blood isolate. Subsequently, we retrospectively (2011-2017) and prospectively (2018-2019) tested patients who had been hospitalized with a similar clinico-biological picture. In addition, as these patients had been in contact with frugivorous bats (authorized under conditions for hunting and eating in New Caledonia), we investigated the role of these animals and their biting flies by testing them for hemotropic mycoplasmas. RESULTS: There were 15 patients found to be infected by this hemotropic mycoplasma. Among them, 4 (27%) died following splenectomy performed either for spontaneous spleen rupture or to cure refractory autoimmune hemolytic anemia. The bacterium was cultivated from the patient's blood. The full genome of the Neocaledonian Candidatus M. haemohominis strain differed from that of a recently identified Japanese strain. Of 40 tested Pteropus bats, 40% were positive; 100% of collected bat flies Cyclopodia horsfieldi (Nycteribiidae, Diptera) were positive. Human, bat, and dipteran strains were highly similar. CONCLUSIONS: The bacterium being widely distributed in bats, Candidatus M. haemohominis, should be regarded as a potential cause of severe infections in humans.


Asunto(s)
Quirópteros , Infecciones por Mycoplasma , Mycoplasma , Animales , Humanos , Mycoplasma/genética , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/veterinaria , Filogenia , Estudios Retrospectivos
3.
Genes Chromosomes Cancer ; 53(1): 52-66, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24249258

RESUMEN

MYC is a potent oncogene involved in ∼70% of human cancers, inducing tumorigenesis with high penetrance and short latency in experimental transgenic models. Accordingly, MYC is recognized as a major driver of T-cell acute lymphoblastic leukemia (T-ALL) in human and zebrafish/mouse models, and uncovering the context by which MYC-mediated malignant transformation initiates and develops remains a considerable challenge. Because MYC is a very complex oncogene, highly dependent on the microenvironment and cell-intrinsic context, we generated transgenic mice (tgMyc(spo)) in which ectopic Myc activation occurs sporadically (<10(-6) thymocytes) within otherwise normal thymic environment, thereby mimicking the unicellular context in which oncogenic alterations initiate human tumors. We show that while Myc(+) clones in tgMyc(spo) mice develop and initially proliferate in thymus and the periphery, no tumor or clonal expansion progress in aging mice (n = 130), suggesting an unexpectedly low ability of Myc to initiate efficient tumorigenesis. Furthermore, to determine the relevance of this observation in human pathogenesis we analyzed a human T-ALL case at diagnosis and relapse using the molecular stigmata of V(D)J recombination as markers of malignant progression; we similarly demonstrate that despite the occurrence of TAL1 and MYC translocations in early thymocyte ontogeny, subsequent oncogenic alterations were required to drive oncogenesis. Altogether, our data suggest that although central to T-ALL, MYC overexpression per se is inefficient in triggering the cascade of events leading to malignant transformation.


Asunto(s)
Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Genes myc/fisiología , Péptidos y Proteínas de Señalización Intracelular/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Animales , Crisis Blástica/genética , Crisis Blástica/patología , Células HeLa , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Ratones , Ratones Transgénicos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Recurrencia , Translocación Genética , Recombinación V(D)J
4.
Emerg Microbes Infect ; 10(1): 536-544, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33686914

RESUMEN

Compared to the previous 2013-2014 outbreak, dengue 2016-2017 outbreak in New Caledonia was characterized by an increased number of severe forms associated with hepatic presentations. In this study, we assessed the virological factors associated with this enhanced severity. Whole-genome sequences were retrieved from dengue virus (DENV)-1 strains collected in 2013-2014 and from severe and non-severe patients in 2016-2017. Fitness, hepatic tropism and cytopathogenicity of DENV 2016-2017 strains were compared to those of 2013-2014 strains using replication kinetics in the human hepatic cell line HuH7. Whole-genome sequencing identified four amino acid substitutions specific to 2016-2017 strains and absent from 2013-2014 strains. Three of these mutations occurred in predicted T cell epitopes, among which one was also a B cell epitope. Strains retrieved from severe forms did not exhibit specific genetic features. DENV strains from 2016-2017 exhibited a trend towards reduced replicative fitness and cytopathogenicity in vitro compared to strains from 2013-2014. Overall, the 2016-2017 dengue outbreak in New Caledonia was associated with a viral genetic evolution which had limited impact on DENV hepatic tropism and cytopathogenicity. These mutations, however, may have modified DENV strains antigenicity, altering the anti-DENV immune response in some patients, in turn favoring the development of severe forms.Trial registration: ClinicalTrials.gov identifier: NCT04615364.


Asunto(s)
Virus del Dengue/genética , Virus del Dengue/patogenicidad , Dengue/epidemiología , Dengue/virología , Evolución Molecular , Hepatitis/virología , Sustitución de Aminoácidos , Animales , Línea Celular , Dengue/inmunología , Virus del Dengue/inmunología , Brotes de Enfermedades , Variación Genética , Genoma Viral , Genotipo , Humanos , Mutación , Nueva Caledonia/epidemiología , Filogenia , ARN Viral , Análisis de Secuencia de ARN , Índice de Severidad de la Enfermedad , Replicación Viral , Secuenciación Completa del Genoma
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