Nanoparticle-Based Vaccines against Zoonotic Viruses: A Review

Vaccines are the most promising tools for maintaining public health. Most emerging human infectious diseases are caused by viruses originating from an animal reservoir via zoonotic transmission. Therefore, zoonotic virus spillover and spread in humans have become global health threats. Nanoparticle-based vaccines are ideal for antigen delivery, as adjuvants, and as viral structure mimics. Nanoparticles benefit vaccine design and are utilized to protect the antigen cargo, and increase the immunogenicity and efficacy. Therefore, nanoparticle vaccines are a novel method of immunization by which optimal immune responses are elicited. Herein we review current approaches in the development of nanoparticle vaccines and highlight the role of nanoparticle vaccines against zoonotic viral diseases

Comprehensive meta-analysis reveals the impact of non-biodegradable plastic pollution on methane production in anaerobic digestion

Plastics as emerging contaminants have been heavily accumulated in organic wastes (e.g. waste activated sludge and food waste), which have a dramatically different impact on the resource recovery from these organic wastes through anaerobic digestion. However, the reported studies differ significantly from each other, and a comprehensive analysis to reveal the complex effects of plastic pollution in organic wastes on methane production is still lacking. In this study, 28 articles were selected from three citation databases for meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines. Subgroup analysis was then performed to determine the effects of plastic type, particle size, and concentration on methane production and multiple physicochemical parameters. The meta-analysis showed that the mean effect size of plastic pollution on methane production was 0.93 [0.89, 0.98] (p < 0.05). The results also revealed that the presence of plastics negatively affected the organic content and enzyme activity, as well as increasing the reactive oxygen species. In addition, the effect of nanoplastics on these physicochemical parameters was more significant compared to microplastics, like highlighted by most studies. Finally, structural equation modelling quantified that plastic pollution affected methane production by two main pathways: inhibition of organic solubilisation and induction of reactive oxygen species. This information is helpful to a more profound understanding the underlying toxicity mechanisms of plastic pollution to methane production and provide guidance for future research

Functionally Orthologous Viral and Cellular MicroRNAs Studied by a Novel Dual-Fluorescent Reporter System

Recent research raised the possibility that some viral microRNAs (miRNAs) may function as orthologs of cellular miRNAs. In the present work, to study the functional orthologous relationships of viral and cellular miRNAs, we first constructed a dual-fluorescent protein reporter vector system for the easy determination of miRNA function. By expressing the miRNAs and the indicator and internal control fluorescent proteins individually from a single vector, this simple reporter system can be used for miRNA functional assays that include visualizing miRNA activity in live cells. Sequence alignments indicated that the simian virus 40 (SV40) encoded miRNA sv40-mir-S1-5p contains a seed region identical to that of the human miRNA hsa-miR423-5p. Using the new reporter system, it was found that sv40-mir-S1-5p and hsa-miR423-5p downregulate the expression of common artificial target mRNAs and some predicted biological targets of hsa-miR423-5p, demonstrating that they are functional orthologs. The human immunodeficiency virus 1 (HIV-1) encoded hiv1-miR-N367 also contains a seed sequence identical to that of the human miRNA hsa-miR192. Functional assays showed that hiv1-miR-N367 and hsa-miR192 could downregulate common artificial and predicted biological targets, suggesting that these miRNAs may also act as functional orthologs. Thus, this study presents a simple and universal system for testing miRNA function and identifies two new pairs of functional orthologs, sv40-mir-S1-5p and hsa-miR423-5p as well as hiv-1-miR-N367 and hsa-miR192. These findings also expand upon our current knowledge of functional homology and imply that a more general phenomenon of orthologous relationships exists between viral and cellular miRNAs

Target density effects on charge tansfer of laser-accelerated carbon ions in dense plasma

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft X-ray regime. We used the tri-cellulose acetate (C$_{9}$H$_{16}$O$_{8}$) foam of 2 mg/cm$^{-3}$ density, and $1$-mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. The plasma parameters were diagnosed to be T$_{e}$=17 eV and n$_{e}$=4 $\times$ 10$^{20}$ cm$^{-3}$. The average charge states passing through the plasma were observed to be higher than those predicted by the commonly-used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. In previsous measurement with partially ionized plasma from gas discharge and z-pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we were able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-Glass laser radiation. The finding is important for heavy ion beam driven high energy density physics and fast ignitions.Comment: 7 pages, 4 figures, 35 conference

Ebola virus disrupts the inner blood-retinal barrier by induction of vascular endothelial growth factor in pericytes

Ebola virus (EBOV) causes severe hemorrhagic fever in humans with high mortality. In Ebola virus disease (EVD) survivors, EBOV persistence in the eyes may break through the inner blood–retinal barrier (iBRB), leading to ocular complications and EVD recurrence. However, the mechanism by which EBOV affects the iBRB remains unclear. Here, we used the in vitro iBRB model to simulate EBOV in retinal tissue and found that Ebola virus-like particles (EBO-VLPs) could disrupt the iBRB. Cytokine screening revealed that EBO-VLPs stimulate pericytes to secrete vascular endothelial growth factor (VEGF) to cause iBRB breakdown. VEGF downregulates claudin-1 to disrupt the iBRB. Ebola glycoprotein is crucial for VEGF stimulation and iBRB breakdown. Furthermore, EBO-VLPs caused iBRB breakdown by stimulating VEGF in rats. This study provides a mechanistic insight into that EBOV disrupts the iBRB, which will assist in developing new strategies to treat EBOV persistence in EVD survivors. Author summary Ebola virus (EBOV) persistence in eyes has been frequently reported and has become an enormous international public health challenge. EBOV persistence in the eyes may break through the inner blood–retinal–barrier (iBRB), leading to ocular complications and EBOV recurrence. However, the mechanism by which EBOV affects the iBRB remains unclear. Here, we found that Ebola virus-like particles stimulate retinal pericytes to secrete vascular endothelial growth factor (VEGF) to cause iBRB breakdown. VEGF causes iBRB breakdown by disrupting the tight junction protein claudin-1. Ebola glycoprotein plays a key role in VEGF stimulation and iBRB breakdown. Our study provides a mechanistic insight into that EBOV disrupts the iBRB, which will assist in developing new strategies to treat EBOV persistence in EBOV survivors

Fleshy-fruited species increase with elevation for woody lianas but peak in mid-elevations for herbaceous vines in a subtropical forest system

Fruit type composition (dry or fleshy) can substantially influence plant community function. Many studies have researched how fruit type changes with elevation gradient in montane regions; however, these data are lacking for climbing plants. Climbing plants have unique functional traits and requirements, determined by a diversity of factors. Here we analyzed the fruit type produced by 245 climbing plant species collected along a 3-km elevational gradient in a subtropical forest ecosystem in China. We found that woody lianas showed a monotonic increase (McFadden's R-2 = 0.164) in the proportion of fleshy-fruited species, while herbaceous vines showed a unimodal pattern (McFadden's R-2 = 0.080). The results remained consistent after taking phylogenetic correlation among species into account. This clear relationship suggests that for climbing plants the change in various environmental factors with elevation is the main driver of the proportion of fleshy-fruited species. Understanding which factors and mechanisms underpin climbing plant fruit types, and thus seed dispersal dynamics, is not only important for conceptual ecology, but also for conservation and predicting forest composition under global change

The tegument protein UL94 of human cytomegalovirus as a binding partner for tegument protein pp28 identified by intracellular imaging

AbstractThe tegument protein pp28 of human cytomegalovirus (HCMV) is essential for the assembly of infectious HCMV virions, but how it functions during the process of HCMV tegumentation and envelopment remains unclear. By using live cell fluorescence resonance energy transfer (FRET) microscopy and yeast two-hybrid assays, we found that another HCMV tegument protein, UL94, was a specific binding partner for pp28. The interaction between pp28 and UL94 was imaged in a punctuate, juxtanuclear compartment, previously designated as the virus assembly compartment (AC). Amino acids 22–43 of pp28 were identified as being responsible for its binding with UL94, while no linear binding site could be found within UL94. The interaction between pp28 and UL94 may serve as a link in the sequential processes of HCMV capsidation, tegumentation and envelopment. This study provides a foundation for further studies into how the HCMV tegument proteins act in the assembly of HCMV virions

Ebola Virus Uptake into Polarized Cells from the Apical Surface

Ebola virus (EBOV) causes severe hemorrhagic fever with high mortality rates. EBOV can infect many types of cells. During severe EBOV infection, polarized epithelial and endothelial cells are damaged, which promotes vascular instability and dysregulation. However, the mechanism causing these symptoms is largely unknown. Here, we studied virus infection in polarized Vero C1008 cells grown on semipermeable Transwell by using EGFP-labeled Ebola virus-like particles (VLPs). Our results showed that Ebola VLPs preferred to enter polarized Vero cells from the apical cell surface. Furthermore, we showed that the EBOV receptors TIM-1 and Axl were distributed apically, which could be responsible for mediating efficient apical viral entry. Macropinocytosis and intracellular receptor Niemann&ndash;Pick type C1 (NPC1) had no polarized distribution, although they played roles in virus entry. This study provides a new view of EBOV uptake and cell polarization, which facilitates a further understanding of EBOV infection and pathogenesis

Effects of Microtubule Modulators on HIV-1 Infection of Transformed and Resting CD4 T Cells ▿

Previous studies have observed fluorescently labeled HIV particles tracking along microtubule networks for nuclear localization. To provide direct evidence for the involvement of microtubules in early steps of HIV infection of human CD4 T cells, we used multiple microtubule modulators such as paclitaxel (originally called taxol; 1 μM), vinblastine (1 and 10 μM), colchicine (10 and 100 μM), and nocodazole (10 and 100 μM) to disturb microtubule networks in transformed and resting CD4 T cells. Although these drugs disrupted microtubule integrity, almost no inhibition of HIV-1 infection was observed. Our results do not appear to support an essential role for microtubules in the initiation of HIV infection of CD4 T cells

Seed dispersers shape the pulp nutrients of fleshy-fruited plants

The dispersal-syndrome hypothesis posits that fruit traits are a product of selection by frugivores. Although criticized as adaptationist, recent studies have suggested that traits such as fruit or seed size, colour and odour exhibit signatures that imply selection by animal mutualists. These traits imply nutritional rewards (e.g. lipid, carbohydrate), attracting frugivores; however, this remains incompletely resolved. Here, we investigated whether fruit nutrients (lipid, sugar, protein, vitamin C, water content) moderate the co-adaptation of key disperser-group mutualisms. Multivariate techniques revealed that fruit nutrients assembled non-randomly and grouped according to key dispersal modes. Bird-dispersed fruits were richer in lipids than mammal-dispersed fruits. Mixed-dispersed fruits had significantly higher vitamin C than did mammal- or bird-dispersed fruits separately. Sugar and water content were consistently high irrespective of dispersal modes, suggesting that these traits appeal to both avian and mammalian frugivores to match high-energy requirements. Similarly, protein content was low irrespective of dispersal modes, corroborating that birds and mammals avoid protein-rich fruits, which are often associated with toxic levels of nitrogenous secondary compounds. Our results provide substantial over-arching evidence that seed disperser assemblages co-exert fundamental selection pressures on fruit nutrient trait adaptation, with broad implications for structuring fruit-frugivore mutualism and maintaining fruit trait diversity