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1.
Nat Commun ; 15(1): 1236, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336944

RESUMO

The mosquito-borne disease, Yellow fever (YF), has been largely controlled via mass delivery of an effective vaccine and mosquito control interventions. However, there are warning signs that YF is re-emerging in both Sub-Saharan Africa and South America. Imported from Africa in slave ships, YF was responsible for devastating outbreaks in the Caribbean. In Martinique, the last YF outbreak was reported in 1908 and the mosquito Aedes aegypti was incriminated as the main vector. We evaluated the vector competence of fifteen Ae. aegypti populations for five YFV genotypes (Bolivia, Ghana, Nigeria, Sudan, and Uganda). Here we show that mosquito populations from the Caribbean and the Americas were able to transmit the five YFV genotypes, with YFV strains for Uganda and Bolivia having higher transmission success. We also observed that Ae. aegypti populations from Martinique were more susceptible to YFV infection than other populations from neighboring Caribbean islands, as well as North and South America. Our vector competence data suggest that the threat of re-emergence of YF in Martinique and the subsequent spread to Caribbean nations and beyond is plausible.


Assuntos
Aedes , Febre Amarela , Animais , Humanos , Vírus da Febre Amarela/genética , Mosquitos Vetores , Índias Ocidentais , Região do Caribe/epidemiologia , Uganda
2.
Sci Rep ; 12(1): 6973, 2022 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484193

RESUMO

The mosquito Aedes albopictus is an invasive species first detected in Europe in Albania in 1979, and now established in 28 European countries. Temperature is a limiting factor in mosquito activities and in the transmission of associated arboviruses namely chikungunya (CHIKV) and dengue (DENV). Since 2007, local transmissions of CHIKV and DENV have been reported in mainland Europe, mainly in South Europe. Thus, the critical question is how far north transmission could occur. In this context, the Albanian infestation by Ae. albopictus is of interest because the species is present up to 1200 m of altitude; this allows using altitude as a proxy for latitude. Here we show that Ae. albopictus can transmit CHIKV at 28 °C as well as 20 °C, however, the transmission of DENV is only observed at 28 °C. We conclude that if temperature is the key environmental factor limiting transmission, then transmission of CHIKV, but not DENV is feasible in much of Europe.


Assuntos
Aedes , Febre de Chikungunya , Vírus Chikungunya , Dengue , Animais , Temperatura
3.
Rev Med Virol ; 32(4): e2333, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35124859

RESUMO

This last decade has seen a resurgence of yellow fever (YF) in historical endemic regions and repeated attempts of YF introduction in YF-free countries such as the Asia-Pacific region and the Caribbean. Infected travellers are the main entry routes in these regions where competent mosquito vectors proliferate in appropriate environmental conditions. With the discovery of the 17D vaccine, it was thought that YF would be eradicated. Unfortunately, it was not the case and, contrary to dengue, chikungunya and Zika, factors that cotribute to YF transmission remain under investigation. Today, all the signals are red and it is very likely that YF will be the next pandemic in the YF-free regions where millions of people are immunologically naïve. Unlike COVID-19, YF is associated with a high case-fatality rate and a high number of deaths are expected. This review gives an overview of global YF situation, including the non-endemic Asia-Pacific region and the Caribbean where Aedes aegypti is abundantly distributed, and also proposes different hypotheses on why YF outbreaks have not yet occurred despite high records of travellers importing YF into these regions and what role Aedes mosquitoes play in the emergence of urban YF.


Assuntos
Aedes , COVID-19 , Febre de Chikungunya , Febre Amarela , Infecção por Zika virus , Zika virus , Animais , Humanos , Mosquitos Vetores , Febre Amarela/epidemiologia , Vírus da Febre Amarela
4.
Sci Rep ; 10(1): 18404, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33110109

RESUMO

In most of the world, Dengue virus (DENV) is mainly transmitted by the mosquito Aedes aegypti while in Europe, Aedes albopictus is responsible for human DENV cases since 2010. Identifying mutations that make DENV more competent for transmission by Ae. albopictus will help to predict emergence of epidemic strains. Ten serial passages in vivo in Ae. albopictus led to select DENV-1 strains with greater infectivity for this vector in vivo and in cultured mosquito cells. These changes were mediated by multiple adaptive mutations in the virus genome, including a mutation at position 10,418 in the DENV 3'UTR within an RNA stem-loop structure involved in subgenomic flavivirus RNA production. Using reverse genetics, we showed that the 10,418 mutation alone does not confer a detectable increase in transmission efficiency in vivo. These results reveal the complex adaptive landscape of DENV transmission by mosquitoes and emphasize the role of epistasis in shaping evolutionary trajectories of DENV variants.


Assuntos
Adaptação Fisiológica , Aedes/virologia , Vírus da Dengue/fisiologia , Mosquitos Vetores/virologia , Animais , Dengue/epidemiologia , Dengue/transmissão , Epistasia Genética , Humanos
7.
Emerg Microbes Infect ; 8(1): 1265-1279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31469046

RESUMO

Since its genome details are publically available, the mosquito Aedes albopictus has become the central stage of attention for deciphering multiple biological and evolutionary aspects at the root of its success as an invasive species. Its genome of 1,967 Mb harbours an unusual high number of non-retroviral integrated RNA virus sequences (NIRVS). NIRVS are enriched in piRNA clusters and produce piRNAs, suggesting an antiviral effect. Here, we investigated the evolutionary history of NIRVS in geographically distant Ae. albopictus populations by comparing genetic variation as derived by neutral microsatellite loci and seven selected NIRVS. We found that the evolution of NIRVS was far to be neutral with variations both in their distribution and sequence polymorphism among Ae. albopictus populations. The Flaviviral elements AlbFlavi2 and AlbFlavi36 were more deeply investigated in their association with dissemination rates of dengue virus (DENV) and chikungunya virus (CHIKV) in Ae. albopictus at both population and individual levels. Our results show a complex association between NIRVS and DENV/CHIKV opening a new avenue for investigating the functional role of NIRVS as antiviral elements shaping vector competence of mosquitoes to arboviruses.


Assuntos
Aedes/genética , Evolução Molecular , Flaviviridae/genética , Genoma de Inseto , Mosquitos Vetores/genética , Aedes/imunologia , Aedes/virologia , Animais , Vírus Chikungunya/isolamento & purificação , Vírus da Dengue/isolamento & purificação , Mosquitos Vetores/imunologia , Mosquitos Vetores/virologia , RNA Interferente Pequeno/genética
8.
Gut ; 68(4): 693-707, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30415234

RESUMO

OBJECTIVE: Pancreatic cancer is associated with an abundant stromal reaction leading to immune escape and tumour growth. This massive stroma drives the immune escape in the tumour. We aimed to study the impact of ßig-h3 stromal protein in the modulation of the antitumoural immune response in pancreatic cancer. DESIGN: We performed studies with p48-Cre;KrasG12D, pdx1-Cre;KrasG12D;Ink4a/Arffl/fl, pdx1-Cre;KrasG12D; p53R172H mice and tumour tissues from patients with pancreatic ductal adenocarcinoma (PDA). Some transgenic mice were given injections of anti-ßig-h3, anti-CD8, anti-PD1 depleting antibodies. Tumour growth as well as modifications in the activation of local immune cells were analysed by flow cytometry, immunohistochemistry and immunofluorescence. Tissue stiffness was measured by atomic force microscopy. RESULTS: We identified ßig-h3 stromal-derived protein as a key actor of the immune paracrine interaction mechanism that drives pancreatic cancer. We found that ßig-h3 is highly produced by cancer-associated fibroblasts in the stroma of human and mouse. This protein acts directly on tumour-specific CD8+ T cells and F4/80 macrophages. Depleting ßig-h3 in vivo reduced tumour growth by enhancing the number of activated CD8+ T cell within the tumour and subsequent apoptotic tumour cells. Furthermore, we found that targeting ßig-h3 in established lesions released the tissue tension and functionally reprogrammed F4/80 macrophages in the tumour microenvironment. CONCLUSIONS: Our data indicate that targeting stromal extracellular matrix protein ßig-h3 improves the antitumoural response and consequently reduces tumour weight. Our findings present ßig-h3 as a novel immunological target in pancreatic cancer.


Assuntos
Adenocarcinoma/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma Ductal Pancreático/imunologia , Proteínas da Matriz Extracelular/imunologia , Neoplasias Pancreáticas/imunologia , Fator de Crescimento Transformador beta/imunologia , Microambiente Tumoral/imunologia , Animais , Fibroblastos/imunologia , Citometria de Fluxo , Imunofluorescência , Humanos , Imuno-Histoquímica , Macrófagos/imunologia , Camundongos , Camundongos Transgênicos , Microscopia de Força Atômica , Comunicação Parácrina/imunologia
9.
J Virol ; 89(7): 3484-96, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25568210

RESUMO

UNLABELLED: The RNA genome of respiratory syncytial virus (RSV) is constitutively encapsidated by the viral nucleoprotein N, thus forming a helical nucleocapsid. Polymerization of N along the genomic and antigenomic RNAs is concomitant to replication and requires the preservation of an unassembled monomeric nucleoprotein pool. To this end, and by analogy with Paramyxoviridae and Rhabdoviridae, it is expected that the viral phosphoprotein P acts as a chaperone protein, forming a soluble complex with the RNA-free form of N (N(0)-P complex). Here, we have engineered a mutant form of N that is monomeric, is unable to bind RNA, still interacts with P, and could thus mimic the N(0) monomer. We used this N mutant, designated N(mono), as a substitute for N(0) in order to characterize the P regions involved in the N(0)-P complex formation. Using a series of P fragments, we determined by glutathione S-transferase (GST) pulldown assays that the N and C termini of P are able to interact with N(mono). We analyzed the functional role of amino-terminal residues of P by site-directed mutagenesis, using an RSV polymerase activity assay based on a human RSV minireplicon, and found that several residues were critical for viral RNA synthesis. Using GST pulldown and surface plasmon resonance assays, we showed that these critical residues are involved in the interaction between P[1-40] peptide and N(mono) in vitro. Finally, we showed that overexpression of the peptide P[1-29] can inhibit the polymerase activity in the context of the RSV minireplicon, thus demonstrating that targeting the N(0)-P interaction could constitute a potential antiviral strategy. IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants. Since no vaccine or efficient antiviral treatment is available against RSV, it is essential to better understand how the viral machinery functions in order to develop new antiviral strategies. RSV phosphoprotein P, the main RNA polymerase cofactor, is believed to function as a chaperon protein, maintaining N as a nonassembled, RNA-free protein (N(0)) competent for RNA encapsidation. In this paper, we provide the first evidence, to our knowledge, that the N terminus of P contains a domain that binds specifically to this RNA-free form of N. We further show that overexpression of a small peptide spanning this region of P can inhibit viral RNA synthesis. These findings extend our understanding of the function of RSV RNA polymerase and point to a new target for the development of drugs against this virus.


Assuntos
Proteínas do Nucleocapsídeo/metabolismo , Mapeamento de Interação de Proteínas , Vírus Sincicial Respiratório Humano/fisiologia , Proteínas Estruturais Virais/metabolismo , Animais , Sítios de Ligação , Linhagem Celular , Centrifugação/métodos , Cricetinae , Análise Mutacional de DNA , Mutagênese Sítio-Dirigida , Ligação Proteica , Vírus Sincicial Respiratório Humano/genética , Ressonância de Plasmônio de Superfície , Proteínas Estruturais Virais/genética
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