RESUMEN
The incidence of Leishmania/HIV co-infection is growing and few studies detail the cellular processes and macromolecules participating in co-infection. Thus, the goal of this study was to partially describe the Leishmania/HIV co-infection events by measuring molecular and functional parameters associated with both pathogens in vitro. MT-4 cells (human T-lymphocytes), primary monocytes, and peripheral blood mononuclear cells were exposed to HIV and/or Leishmania donovani. The cytopathic effects generated by the pathogens were observed through microscopy. Viral replication was assessed by monitoring p24 protein levels and parasitic proliferation/infectivity was determined using Giemsa staining. Changes in molecular markers were evaluated by ELISA and fluorescence assays. Our results showed that our system reassembles the main parameters previously described for Leishmania/HIV co-infection in patients in terms of potentiation of parasitic and viral replication/infectivity, amplification of syncytia induction, and alterations of cell viability. In addition, an amplification in NF-κB activation, changes in CXCR4/CCR5 surface expression, and a Th1âTh2 variation in cytokine/chemokine secretion were demonstrated. Altogether, this study could contribute to gain a deep understanding of the molecular events associated with Leishmania/HIV co-infection.
Asunto(s)
Coinfección , Infecciones por VIH , VIH-1 , Leishmania donovani , Infecciones por VIH/complicaciones , VIH-1/fisiología , Humanos , Leucocitos MononuclearesRESUMEN
Recent reports have shown that small and big felines could be infected by SARS-CoV-2, while other animals, like swines and mice, are apparently not susceptible to this infection. These findings raise the question of the role of cell factors associated with early stages of the viral infection in host selectivity. The cellular receptor for SARS-CoV-2 is the Angiotensin Converting Enzyme (ACE2). Transmembrane protease serine 2 (TMPRSS2) has been shown to prime the viral spike for its interaction with its receptor. GRP78 has also been proposed as a possible co-receptor. In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. We selected several mammalian hosts that could play a key role in viral spread by acting as secondary hosts (cats, dogs, pigs, mice, and ferrets) and evaluated their predicted permissiveness by in silico analysis. Results showed that ionic pairs (salt bridges, N-O pair, and long-range interactions) produced between ACE2 and the viral spike has an essential function in the host interaction. On the other hand, TMPRSS2 and GRP78 are proteins with high homology in all the evaluated hosts. Thus, these proteins do not seem to play a role in host selectivity, suggesting that other factors may play a role in the non-permissivity in some of these hosts. These proteins represent however interesting cell targets that could be explored in order to control the virus replication in humans and in the intermediary hosts.
Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/virología , Proteínas de Choque Térmico/química , Mamíferos/metabolismo , Peptidil-Dipeptidasa A/química , Neumonía Viral/virología , Receptores Virales/química , Serina Endopeptidasas/química , Glicoproteína de la Espiga del Coronavirus/metabolismo , Tropismo Viral , Secuencia de Aminoácidos , Enzima Convertidora de Angiotensina 2 , Animales , Antivirales/farmacología , Benzamidinas , COVID-19 , Gatos , Perros , Chaperón BiP del Retículo Endoplásmico , Hurones , Guanidinas/farmacología , Proteínas de Choque Térmico/metabolismo , Humanos , Ratones , Modelos Moleculares , Simulación del Acoplamiento Molecular , Pandemias , Peptidil-Dipeptidasa A/metabolismo , Conformación Proteica , Receptores Virales/metabolismo , SARS-CoV-2 , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Serina Endopeptidasas/metabolismo , Especificidad de la Especie , Porcinos , Acoplamiento Viral , Internalización del VirusRESUMEN
The primary objective of this study was to search for natural products capable of inhibiting hepatitis B virus (HBV) replication. The research design, methods and procedures included testing hydro-alcoholic extracts (n = 66) of 31 species from the Venezuelan Amazonian rain forest on the cell line HepG2 2.2.15, which constitutively produces HBV. The main outcomes and results were as follows: the species Euterpe precatoria, Jacaranda copaia, Jacaranda obtusifolia, Senna silvestris, Warscewiczia coccinea and Vochysia glaberrima exerted some degree of inhibition on HBV replication. The leaves of W. coccinea showed a significant antiviral activity: 80% inhibition with 100 µg mL⻹ of extract. This extract also exerted inhibition on covalently closed circular deoxyribonucleic acid (cccDNA) production and on HIV-1 replication in MT4 cells (more than 90% inhibition with 50 µg mL⻹ of extract). Initial fractionation using organic solvents of increasing polarity and water showed that the ethanol fraction was responsible for most of the antiviral inhibitory activities of both the viruses. It was concluded that Warscewiczia coccinea extract showed inhibition of HBV and HIV-1 replication. Bioassay-guided purification of this fraction may allow the isolation of an antiviral compound with inhibitory activity against both viruses.
Asunto(s)
Antivirales/farmacología , VIH-1/efectos de los fármacos , Virus de la Hepatitis B/efectos de los fármacos , Extractos Vegetales/farmacología , Rubiaceae/química , Replicación Viral/efectos de los fármacos , Línea Celular Transformada , Etanol , Células Hep G2 , Humanos , Factores de TiempoRESUMEN
11-Deoxyfistularin-3 (1), a new bromotyrosine derivative, was isolated among other known compounds such as fistularin-3 (2), aerothionin (3), and 11-oxoaerothionin (4) from the Caribbean sponge Aplysinafistularis (Aplysinellidae). The structure of 1 was determined by spectroscopic analysis and showed in vitro activity against the human breast carcinoma cell line MCF-7.
Asunto(s)
Antineoplásicos/aislamiento & purificación , Poríferos/química , Tirosina/análogos & derivados , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Humanos , Estructura Molecular , Análisis Espectral , Células Tumorales Cultivadas , Tirosina/química , Tirosina/aislamiento & purificación , Tirosina/farmacologíaRESUMEN
Illimaquinone, a sponge metabolite that disrupts the Golgi complex in mammalian cells, stopped proliferation and induced morphological and ultrastructural changes in promastigotes of L. mexicana. Radioactive labeling of proteins demonstrates an increased excretion function and diminution of membrane acid phosphatase activity, due probably to the vesiculation of the Golgi complex and alteration of the cell protein sorting mechanism. The result indicated that illimaquinone could be useful for the study of intracellular traffic in Trypanosomatidae.