scholarly journals Biological Characteristics and Patterns of Codon Usage Evolution for the African Genotype Zika Virus

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1306
Author(s):  
Martin Faye ◽  
Naimah Zein ◽  
Cheikh Loucoubar ◽  
Manfred Weidmann ◽  
Ousmane Faye ◽  
...  
Keyword(s):  
Codon Usage ◽  
Zika Virus ◽  
Yellow Fever Virus ◽  
Temporal Trends ◽  
Biological Properties ◽  
Host Tropism ◽  
Mosquito Cells ◽  
Mosquito Cell Lines ◽  
The Individual

We investigated temporal trends of codon usage changes for different host species to determine their importance in Zika virus (ZIKV) evolution. Viral spillover resulting from the potential of codon adaptation to host genome was also assessed for the African genotype ZIKV in comparison to the Asian genotype. To improve our understanding on its zoonotic maintenance, we evaluated in vitro the biological properties of the African genotype ZIKV in vertebrate and mosquito cell lines. Analyses were performed in comparison to Yellow fever virus (YFV). Despite significantly lower codon adaptation index trends than YFV, ZIKV showed evident codon adaptation to vertebrate hosts, particularly for the green African monkey Chlorocebus aethiops. PCA and CAI analyses at the individual ZIKV gene level for both human and Aedes aegypti indicated a clear distinction between the two genotypes. African ZIKV isolates showed higher virulence in mosquito cells than in vertebrate cells. Their higher replication in mosquito cells than African YFV confirmed the role of mosquitoes in the natural maintenance of the African genotype ZIKV. An analysis of individual strain growth characteristics indicated that the widely used reference strain MR766 replicates poorly in comparison to African ZIKV isolates. The recombinant African Zika virus strain ArD128000*E/NS5 may be a good model to include in studies on the mechanism of host tropism, as it cannot replicate in the tested vertebrate cell line.

scholarly journals In Vitro Inhibition of Zika Virus Replication with Amantadine and Rimantadine Hydrochlorides

2021 ◽  
Vol 12 (3) ◽  
pp. 727-738
Author(s):  
Jorge L. Arias-Arias ◽  
Francisco Vega-Aguilar ◽  
Dihalá Picado-Soto ◽  
Eugenia Corrales-Aguilar ◽  
Gilbert D. Loría
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Influenza A ◽  
Yellow Fever Virus ◽  
Human Infection ◽  
Virus Infections ◽  
Drug Concentrations ◽  
Dose Dependent ◽  
Reference Strains

Zika virus (ZIKV) is a mosquito-borne flavivirus in which human infection became relevant during recent outbreaks in Latin America due to its unrecognized association with fetal neurological disorders. Currently, there are no approved effective antivirals or vaccines for the treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV reference strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the latter. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine the potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across flavivirus, susceptible to be blocked by modified more specific adamantane compounds.

scholarly journals The secretory fate of flavivirus NS1 in mosquito cells is influenced by the caveolin binding domain

2019 ◽  
Author(s):  
Romel Rosales Ramirez ◽  
Juan E. Ludert
Keyword(s):  
Yellow Fever ◽  
Zika Virus ◽  
Yellow Fever Virus ◽  
Binding Domain ◽  
Expression Vectors ◽  
Mosquito Vector ◽  
Structural Protein ◽  
Aromatic Residues ◽  
Secretion Pathway ◽  
Mosquito Cells

ABSTRACTFlaviviruses of major medical importance worldwide such as dengue (DENV), Zika (ZIKV), and yellow fever (YFV) viruses are transmitted by mosquitoes Aedes sp. The non-structural protein 1 (NS1) of these flaviviruses is secreted from the infected cells using different secretion routes depending on the cell and virus nature. The NS1 of DENV and ZIKV contain in the hydrophobic region a conserved caveolin binding domain (CBD) (ΦXXΦXXXXΦ), which is not conserved in YFV NS1. To ascertain the role of the CBD in the secretory route followed by flavivirus NS1, expression vectors for the NS1 of DENV2, ZIKV and YFV were constructed. Using site-directed mutagenesis, substitutions were made in the aromatic residues within CBD; in addition, the full domain was replaced by those of other flaviviruses, creating chimeras in the CBD of NS1. Substitutions of the aromatic residues to Ala or Thr, or CBD chimeras, results in increased sensitivity of NS1 secretion to brefeldin A treatment, indicating a change to a classical secretion pathway. Likewise, the insertion of the DENV/ZIKV CBD into the recombinant Gaussia-Luciferase results in a loss of sensitivity to BFA treatment, in luciferase secretion. These results suggest that the CBD sequence is a molecular determinant for the unconventional secretory route followed by DENV and ZIKV NS1 in mosquito cells. However, the cellular components that recognize the CBD in the NS1 of DENV and ZIKV and redirect them to an unconventional route and if this secretion route confers unique functions to NS1 within the vector mosquito are aspects currently unknown.ImportanceFlaviviruses are an important cause of mosquito borne diseases to humans. We have previously demonstrated that the non-structural protein 1 from dengue and zika virus are secreted efficiently from mosquito cells using an unconventional route, that depends on caveolin and molecular chaperones. In this work, we show evidence indicating that a caveolin binding domain, well conserved and exposed in dengue and Zika virus NS1, but absent in other flaviviruses such as yellow fever virus or West Nile virus, is important in determining the unconventional secretion pathway followed by dengue and zika virus NS1 in mosquito cells. The unique secretory pathway followed by NS1 in mosquito cells may result in distinctive viral-cellular protein associations required to facilitate viral infection in the mosquito vector. To identify viral and cellular elements that could disturb the traffic of dengue and Zika virus NS1 may be important to design of strategies for vector control.

scholarly journals Pharmacological properties of fireweed (Epilobium angustifolium L.) and bioavailability of ellagitannins. A review

2020 ◽  
Vol 66 (1) ◽  
pp. 52-64
Author(s):  
Mariola Dreger ◽  
Artur Adamczak ◽  
Katarzyna Seidler-Łożykowska ◽  
Karolina Wielgus
Keyword(s):  
Prostate Cancer ◽  
Cancer Chemoprevention ◽  
Antimicrobial Activities ◽  
Biological Properties ◽  
Pharmacological Properties ◽  
Beneficial Effects ◽  
Epilobium Angustifolium ◽  
The Individual

SummaryFireweed (Epilobium angustifolium L.) is a well-known medicinal plant traditionally used in the treatment of urogenital diseases, stomach and liver disorders, skin problems, etc. E. angustifolium extracts show anti-androgenic, antiproliferative, cytotoxic, antioxidant, anti-inflammatory, immunomodulatory, and antimicrobial activities. The unique combination of biological properties demonstrated by the results of some studies indicates that fireweed has a positive effect in benign prostatic hyperplasia (BPH) and potentially in the prostate cancer chemoprevention. However, the efficacy of E. angustifolium phytotherapy is still poorly tested in clinical trials, while numerous beneficial effects of extracts have been documented in the in vitro and in vivo tests. Fireweed is rich in polyphenolic compounds, particularly ellagitannins. Currently, polyphenols are considered to be modulators of beneficial gut microbiota. The literature data support the use of ellagitannins in the prostate cancer chemoprevention, but caution is advised due to the highly variable production of urolithins by the individual microbiota. A better understanding of the microbiota’s role and the mechanisms of its action are crucial for an optimal therapeutic effect. This paper aims to summarize and discuss experimental data concerning pharmacological properties of E. angustifolium and bioavailability of ellagitannins – important bioactive compounds of this plant.

scholarly journals Fusion protein is the main determinant of metapneumovirus host tropism

2009 ◽  
Vol 90 (6) ◽  
pp. 1408-1416 ◽  
Author(s):  
Miranda de Graaf ◽  
Eefje J. A. Schrauwen ◽  
Sander Herfst ◽  
Geert van Amerongen ◽  
Albert D. M. E. Osterhaus ◽  
...  
Keyword(s):  
Host Range ◽  
Cell Content ◽  
Main Determinant ◽  
F Protein ◽  
Host Tropism ◽  
Turkey Poults ◽  
The Difference ◽  
The Individual ◽  
Protein Cell

Human metapneumovirus (HMPV) and avian metapneumovirus subgroup C (AMPV-C) infect humans and birds, respectively. This study confirmed the difference in host range in turkey poults, and analysed the contribution of the individual metapneumovirus genes to host range in an in vitro cell-culture model. Mammalian Vero-118 cells supported replication of both HMPV and AMPV-C in contrast to avian quail fibroblast (QT6) cells in which only AMPV-C replicated to high titres. Inoculation of Vero-118 and QT6 cells with recombinant HMPV in which genes were exchanged with those of AMPV-C revealed that the metapneumovirus fusion (F) protein is the main determinant for host tropism. Chimeric viruses in which polymerase complex proteins were exchanged between HMPV and AMPV-C replicated less efficiently compared with HMPV in QT6 cells. Using mini-genome systems, it was shown that exchanging these polymerase proteins resulted in reduced replication and transcription efficiency in QT6 cells. Examination of infected Vero-118 and QT6 cells revealed that viruses containing the F protein of AMPV-C yielded larger syncytia compared with viruses containing the HMPV F protein. Cell-content mixing assays revealed that the F protein of AMPV-C was more fusogenic compared with the F protein of HMPV, and that the F2 region is responsible for the difference observed between AMPV-C and HMPV F-promoted fusion in QT6 and Vero-118 cells. This study provides insight into the determinants of host tropism and membrane fusion of metapneumoviruses.

scholarly journals Characterization of a novel insect-specific flavivirus from Brazil: potential for inhibition of infection of arthropod cells with medically important flaviviruses

2014 ◽  
Vol 95 (12) ◽  
pp. 2796-2808 ◽  
Author(s):  
Joan L. Kenney ◽  
Owen D. Solberg ◽  
Stanley A. Langevin ◽  
Aaron C. Brault
Keyword(s):  
Japanese Encephalitis ◽  
Virus Production ◽  
Inhibitory Effect ◽  
Encephalitis Virus ◽  
Growth Potential ◽  
Conserved Sequence ◽  
Mosquito Cells ◽  
Sequence Elements ◽  
Mosquito Cell Lines

In the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated ‘Nhumirim virus’; NHUV) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential and 3′ untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp.-vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell lines were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3′ UTR indicated NHUV to be most similar to viruses within the yellow fever serogroup and Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared with traditional insect-specific flaviviruses. This suggests that, despite apparently being insect specific, this virus probably diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in a significant reduction in virus production of West Nile virus (WNV), St Louis encephalitis virus (SLEV) and Japanese encephalitis virus. The inhibitory effect was most effective against WNV and SLEV with over a 106-fold and 104-fold reduction in peak titres, respectively.

scholarly journals In Vitro Inhibition of Zika Virus Replication with Amantadine and Rimantadine Hydrochlorides

2021 ◽  
Author(s):  
Jorge L. Arias-Arias ◽  
Francisco Vega-Aguilar ◽  
Dihalá Picado-Soto ◽  
Eugenia Corrales-Aguilar ◽  
Gilbert D. Loría
Keyword(s):  
Antiviral Activity ◽  
Zika Virus ◽  
Influenza A ◽  
High Selectivity ◽  
Yellow Fever Virus ◽  
Human Infection ◽  
Virus Infections ◽  
Drug Concentrations ◽  
Dose Dependent

Zika virus (ZIKV) is a mosquito-born flavivirus which human infection became relevant dur-ing recent outbreaks in Latin America, due to its unrecognized association with fetal neurologi-cal disorders. Currently there are no approved effective antivirals or vaccines for treatment or prevention of ZIKV infections. Amantadine and rimantadine are approved antivirals used against susceptible influenza A virus infections, that have been shown to have antiviral activity against other viruses, such as dengue virus (DENV). Here, we report the in vitro effectiveness of both amantadine and rimantadine hydrochlorides against ZIKV replication, resulting in a dose-dependent reduction in viral titers of a ZIKV clinical isolate and two different ZIKV refer-ence strains. Additionally, we demonstrate similar in vitro antiviral activity of these drugs against DENV-1 and yellow fever virus (YFV), although at higher drug concentrations for the later. ZIKV replication was inhibited at drug concentrations well below cytotoxic levels of both compounds, as denoted by the high selectivity indexes obtained with the tested strains. Further work is absolutely needed to determine a potential clinical use of these antivirals against ZIKV infections, but our results suggest the existence of a highly conserved mechanism across fla-vivirus, susceptible to be blocked by modified more specific adamantane compounds.

scholarly journals Species-specific disruption of STING-dependent antiviral cellular defenses by the Zika virus NS2B3 protease

2018 ◽  
Vol 115 (27) ◽  
pp. E6310-E6318 ◽  
Author(s):  
Qiang Ding ◽  
Jenna M. Gaska ◽  
Florian Douam ◽  
Lei Wei ◽  
David Kim ◽  
...  
Keyword(s):  
Zika Virus ◽  
Yellow Fever Virus ◽  
Rna Virus ◽  
Mice Model ◽  
Zikv Infection ◽  
Host Tropism ◽  
Virus West Nile ◽  
Cellular Defenses ◽  
Species Specific

The limited host tropism of numerous viruses causing disease in humans remains incompletely understood. One example is Zika virus (ZIKV), an RNA virus that has reemerged in recent years. Here, we demonstrate that ZIKV efficiently infects fibroblasts from humans, great apes, New and Old World monkeys, but not rodents. ZIKV infection in human—but not murine—cells impairs responses to agonists of the cGMP-AMP synthase/stimulator of IFN genes (cGAS/STING) signaling pathway, suggesting that viral mechanisms to evade antiviral defenses are less effective in rodent cells. Indeed, human, but not mouse, STING is subject to cleavage by proteases encoded by ZIKV, dengue virus, West Nile virus, and Japanese encephalitis virus, but not that of yellow fever virus. The protease cleavage site, located between positions 78/79 of human STING, is only partially conserved in nonhuman primates and rodents, rendering these orthologs resistant to degradation. Genetic disruption of STING increases the susceptibility of mouse—but not human—cells to ZIKV. Accordingly, expression of only mouse, not human, STING in murine STING knockout cells rescues the ZIKV suppression phenotype. STING-deficient mice, however, did not exhibit increased susceptibility, suggesting that other redundant antiviral pathways control ZIKV infection in vivo. Collectively, our data demonstrate that numerous RNA viruses evade cGAS/STING-dependent signaling and affirm the importance of this pathway in shaping the host range of ZIKV. Furthermore, our results explain—at least in part—the decreased permissivity of rodent cells to ZIKV, which could aid in the development of mice model with inheritable susceptibility to ZIKV and other flaviviruses.

In vitro Behaviour of Alumina-Hydroxiapatite Composites Coatings

2018 ◽  
Vol 69 (6) ◽  
pp. 1416-1418
Author(s):  
Alexandru Szabo ◽  
Ilare Bordeasu ◽  
Ion Dragos Utu ◽  
Ion Mitelea
Keyword(s):  
Pure Titanium ◽  
Titanium Substrate ◽  
High Strength ◽  
Biological Properties ◽  
Commercially Pure Titanium ◽  
Hvof Spraying ◽  
Before And After ◽  
Sbf Solution ◽  
Oxygen Fuel

Hydroxyapatite (HA) is a very common material used for biomedical applications. Usually, in order to improve its poor mechanical properties is combined or coated with other high-strength materials.The present paper reports the manufacturing and the biocompatibility behaviour of two different biocomposite coatings consisting of alumina (Al2O3) and hydroxyapatite (HA) using the high velocity oxygen fuel (HVOF) spraying method which were deposited onto the surface of a commercially pure titanium substrate. The biological properties of the Al2O3-HA materials were evaluated by in vitro studies. The morphology of the coatings before and after their immersing in the simulated body fluid (SBF) solution was characterized by scanning electron microscopy (SEM). The results showed an important germination of the biologic hydroxyapatite crystallite on the surface of both coatings.

Nanodrugs as a new approach in therapy of cardiovascular diseases and cancer with tumor-associated angiogenesis

2020 ◽  
Vol 28 ◽  
Author(s):  
Justyna Hajtuch ◽  
Karolina Niska ◽  
Iwona Inkielewicz-Stepniak
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Controlled Drug Release ◽  
Biological Properties ◽  
Comprehensive Information ◽  
Conventional Drug ◽  
Key Factor ◽  
Functionalized Materials

Background: Cancer along with cardiovascular diseases are globally defined as leading causes of death. Importantly, some risk factors are common to these diseases. The process of angiogenesis and platelets aggregation are observed in cancer development and progression. In recent years, studies have been conducted on nanodrugs in these diseases that have provided important information on the biological and physicochemical properties of nanoparticles. Their attractive features are that they are made of biocompatible, well-characterized and easily functionalized materials. Unlike conventional drug delivery, sustained and controlled drug release can be obtained by using nanomaterials. Methods: In this article, we review the latest research to provide comprehensive information on nanoparticle-based drugs for the treatment of cancer, cardiovascular disease associated with abnormal haemostasis, and the inhibition of tumorassociated angiogenesis. Results: The results of the analysis of data based on nanoparticles with drugs confirm their improved pharmaceutical and biological properties, which gives promising antiplatelet, anticoagulant and antiangiogenic effects. Moreover, the review included in vitro, in vivo research and presented nanodrugs with chemotherapeutics approved by Food and Drug Administration. Conclusion: By the optimization of nanoparticles size and surface properties, nanotechnology are able to deliver drugs with enhanced bioavailability in treatment of cardiovascular disease, cancer and inhibition of cancer-related angiogenesis. Thus, nanotechnology can improve the therapeutic efficacy of the drug, but there is a need for a better understanding of the nanodrugs interaction in the human body, because this is a key factor in the success of potential nanotherapeutics.

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