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1.
Emerg Microbes Infect ; 12(1): 2164216, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36580440

RESUMO

Ebolaviruses cause outbreaks of haemorrhagic fever in Central and West Africa. Some members of this genus such as Ebola virus (EBOV) are highly pathogenic, with case fatality rates of up to 90%, whereas others such as Reston virus (RESTV) are apathogenic for humans. Bombali virus (BOMV) is a novel ebolavirus for which complete genome sequences were recently found in free-tailed bats, although no infectious virus could be isolated. Its pathogenic potential for humans is unknown. To address this question, we first determined whether proteins encoded by the available BOMV sequence found in Chaerephon pumilus were functional in in vitro assays. The correction of an apparent sequencing error in the glycoprotein based on these data then allowed us to generate infectious BOMV using reverse genetics and characterize its infection of human cells. Furthermore, we used HLA-A2-transgenic, NOD-scid-IL-2γ receptor-knockout (NSG-A2) mice reconstituted with human haematopoiesis as a model to evaluate the pathogenicity of BOMV in vivo in a human-like immune environment. These data demonstrate that not only does BOMV show a slower growth rate than EBOV in vitro, but it also shows low pathogenicity in humanized mice, comparable to previous studies using RESTV. Taken together, these findings suggest a low pathogenic potential of BOMV for humans.


Assuntos
Ebolavirus , Doença pelo Vírus Ebola , Humanos , Animais , Camundongos , Ebolavirus/genética , Camundongos Endogâmicos NOD , Animais Geneticamente Modificados , África Ocidental
2.
Antiviral Res ; 176: 104749, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32081740

RESUMO

Flaviviruses constitute a public health concern because of their global burden and the lack of specific antiviral treatment. Here we investigated the antiviral activity of the alkaloid anisomycin against dengue (DENV) and Zika (ZIKV) viruses. At non-cytotoxic concentrations, anisomycin strongly inhibited the replication of reference strains and clinical isolates of all DENV serotypes and Asian and African strains of ZIKV in Vero cells. Anisomycin also prevented DENV and ZIKV multiplication in human cell lines. While initial steps of DENV and ZIKV replicative cycle were unaffected, a high inhibition of viral protein expression was demonstrated after treatment with anisomycin. DENV RNA synthesis was strongly reduced in anisomycin treated cultures, but the compound did not exert a direct inhibitory effect on 2' O-methyltransferase or RNA polymerase activities of DENV NS5 protein. Furthermore, anisomycin-mediated activation of p38 signaling was not related to the antiviral action of the compound. The evaluation of anisomycin efficacy in a mouse model of ZIKV morbidity and mortality revealed that animals treated with a low dose of anisomycin exhibited a significant reduction in viremia levels and died significantly later than the control group. This protective effect was lost at higher doses, though. In conclusion, anisomycin is a potent and selective in vitro inhibitor of DENV and ZIKV that impairs a post-entry step of viral replication; and a low-dose anisomycin treatment may provide some minimal benefit in a mouse model.


Assuntos
Anisomicina/farmacologia , Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Zika virus/efeitos dos fármacos , Células A549 , Animais , Chlorocebus aethiops , Dengue/tratamento farmacológico , Dengue/virologia , Vírus da Dengue/fisiologia , Feminino , Humanos , Masculino , Camundongos , Células Vero , Zika virus/fisiologia , Infecção por Zika virus/tratamento farmacológico , Infecção por Zika virus/virologia
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