scholarly journals Sulfated Glycans and Related Digestive Enzymes in the Zika Virus Infectivity: Potential Mechanisms of Virus-Host Interaction and Perspectives in Drug Discovery

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Vitor H. Pomin
Keyword(s):  
Neural Development ◽  
Zika Virus ◽  
Molecular Mechanisms ◽  
Surface Proteins ◽  
Host Cells ◽  
Future Research ◽  
Virus Infectivity ◽  
Virus Attachment ◽  
Chemical Structures ◽  
Host Interaction

As broadly reported, there is an ongoing Zika virus (ZIKV) outbreak in countries of Latin America. Recent findings have demonstrated that ZIKV causes severe defects on the neural development in fetuses in utero and newborns. Very little is known about the molecular mechanisms involved in the ZIKV infectivity. Potential therapeutic agents are also under investigation. In this report, the possible mechanisms of action played by glycosaminoglycans (GAGs) displayed at the surface proteoglycans of host cells, and likely in charge of interactions with surface proteins of the ZIKV, are highlighted. As is common for the most viruses, these sulfated glycans serve as receptors for virus attachment onto the host cells and consequential entry during infection. The applications of (1) exogenous sulfated glycans of different origins and chemical structures capable of competing with the virus attachment receptors (supposedly GAGs) and (2) GAG-degrading enzymes able to digest the virus attachment receptors on the cells may be therapeutically beneficial as anti-ZIKV. This communication attempts, therefore, to offer some guidance for the future research programs aimed to unveil the molecular mechanisms underlying the ZIKV infectivity and to develop therapeutics capable of decreasing the devastating consequences caused by ZIKV outbreak in the Americas.

scholarly journals Zika Virus Trafficking and Interactions in the Human Male Reproductive Tract

Pathogens ◽  
2018 ◽  
Vol 7 (2) ◽  
pp. 51 ◽  
Author(s):  
Lucia Da Silva
Keyword(s):  
Zika Virus ◽  
Reproductive Tract ◽  
Sexual Transmission ◽  
Host Cells ◽  
Future Research ◽  
Mosquito Vector ◽  
Male Reproductive Tract ◽  
Unprotected Sexual Intercourse ◽  
Human Male ◽  
Viral Interactions

Sexual transmission of Zika virus (ZIKV) is a matter of great concern. Infectious viral particles can be shed in semen for as long as six months after infection and can be transferred to male and female sexual partners during unprotected sexual intercourse. The virus can be found inside spermatozoa and could be directly transferred to the oocyte during fertilization. Sexual transmission of ZIKV can contribute to the rise in number of infected individuals in endemic areas as well as in countries where the mosquito vector does not thrive. There is also the possibility, as has been demonstrated in mouse models, that the vaginal deposition of ZIKV particles present in semen could lead to congenital syndrome. In this paper, we review the current literature to understand ZIKV trafficking from the bloodstream to the human male reproductive tract and viral interactions with host cells in interstitial spaces, tubule walls, annexed glands and semen. We hope to highlight gaps to be filled by future research and potential routes for vaccine and antiviral development.

scholarly journals Elucidating the Mechanisms Underlying Enhanced Drought Tolerance in Plants Mediated by Arbuscular Mycorrhizal Fungi

2021 ◽  
Vol 12 ◽  
Author(s):  
Shen Cheng ◽  
Ying-Ning Zou ◽  
Kamil Kuča ◽  
Abeer Hashem ◽  
Elsayed Fathi Abd_Allah ◽  
...  
Keyword(s):  
Drought Stress ◽  
Drought Tolerance ◽  
Mycorrhizal Fungi ◽  
Host Plants ◽  
Molecular Mechanisms ◽  
Arbuscular Mycorrhizal ◽  
Am Fungi ◽  
Host Cells ◽  
Future Research ◽  
Symbiotic Association

Plants are often subjected to various environmental stresses during their life cycle, among which drought stress is perhaps the most significant abiotic stress limiting plant growth and development. Arbuscular mycorrhizal (AM) fungi, a group of beneficial soil fungi, can enhance the adaptability and tolerance of their host plants to drought stress after infecting plant roots and establishing a symbiotic association with their host plant. Therefore, AM fungi represent an eco-friendly strategy in sustainable agricultural systems. There is still a need, however, to better understand the complex mechanisms underlying AM fungi-mediated enhancement of plant drought tolerance to ensure their effective use. AM fungi establish well-developed, extraradical hyphae on root surfaces, and function in water absorption and the uptake and transfer of nutrients into host cells. Thus, they participate in the physiology of host plants through the function of specific genes encoded in their genome. AM fungi also modulate morphological adaptations and various physiological processes in host plants, that help to mitigate drought-induced injury and enhance drought tolerance. Several AM-specific host genes have been identified and reported to be responsible for conferring enhanced drought tolerance. This review provides an overview of the effect of drought stress on the diversity and activity of AM fungi, the symbiotic relationship that exists between AM fungi and host plants under drought stress conditions, elucidates the morphological, physiological, and molecular mechanisms underlying AM fungi-mediated enhanced drought tolerance in plants, and provides an outlook for future research.

scholarly journals Sensing, Signaling, and Secretion: A Review and Analysis of Systems for Regulating Host Interaction in Wolbachia

Genes ◽  
2020 ◽  
Vol 11 (7) ◽  
pp. 813 ◽  
Author(s):  
Amelia R. I. Lindsey
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Molecular Mechanisms ◽  
Host Cells ◽  
Promising Candidate ◽  
Regulate Gene Expression ◽  
Host Interaction ◽  
Female Germline ◽  
Intracellular Infections ◽  
Regulate Gene

Wolbachia (Anaplasmataceae) is an endosymbiont of arthropods and nematodes that resides within host cells and is well known for manipulating host biology to facilitate transmission via the female germline. The effects Wolbachia has on host physiology, combined with reproductive manipulations, make this bacterium a promising candidate for use in biological- and vector-control. While it is becoming increasingly clear that Wolbachia’s effects on host biology are numerous and vary according to the host and the environment, we know very little about the molecular mechanisms behind Wolbachia’s interactions with its host. Here, I analyze 29 Wolbachia genomes for the presence of systems that are likely central to the ability of Wolbachia to respond to and interface with its host, including proteins for sensing, signaling, gene regulation, and secretion. Second, I review conditions under which Wolbachia alters gene expression in response to changes in its environment and discuss other instances where we might hypothesize Wolbachia to regulate gene expression. Findings will direct mechanistic investigations into gene regulation and host-interaction that will deepen our understanding of intracellular infections and enhance applied management efforts that leverage Wolbachia.

scholarly journals Cellular Electron Cryo-Tomography to Study Virus-Host Interactions

2020 ◽  
Vol 7 (1) ◽  
pp. 239-262
Author(s):  
Emmanuelle R.J. Quemin ◽  
Emily A. Machala ◽  
Benjamin Vollmer ◽  
Vojtěch Pražák ◽  
Daven Vasishtan ◽  
...  
Keyword(s):  
Viral Entry ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Virus Assembly ◽  
Three Dimensional ◽  
Surface Proteins ◽  
Host Cells ◽  
Phase Plate ◽  
Structural Cell ◽  
Host Interactions

Viruses are obligatory intracellular parasites that reprogram host cells upon infection to produce viral progeny. Here, we review recent structural insights into virus-host interactions in bacteria, archaea, and eukaryotes unveiled by cellular electron cryo-tomography (cryoET). This advanced three-dimensional imaging technique of vitreous samples in near-native state has matured over the past two decades and proven powerful in revealing molecular mechanisms underlying viral replication. Initial studies were restricted to cell peripheries and typically focused on early infection steps, analyzing surface proteins and viral entry. Recent developments including cryo-thinning techniques, phase-plate imaging, and correlative approaches have been instrumental in also targeting rare events inside infected cells. When combined with advances in dedicated image analyses and processing methods, details of virus assembly and egress at (sub)nanometer resolution were uncovered. Altogether, we provide a historical and technical perspective and discuss future directions and impacts of cryoET for integrative structural cell biology analyses of viruses.

scholarly journals Brain-Derived Neurotrophic Factor in Central Nervous System Myelination: A New Mechanism to Promote Myelin Plasticity and Repair

2018 ◽  
Vol 19 (12) ◽  
pp. 4131 ◽  
Author(s):  
Jessica Fletcher ◽  
Simon Murray ◽  
Junhua Xiao
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neural Development ◽  
Neurotrophic Factor ◽  
Molecular Mechanisms ◽  
Demyelinating Disease ◽  
Cell Types ◽  
Brain Derived Neurotrophic Factor ◽  
Future Research ◽  
Health And Disease

Brain-derived neurotrophic factor (BDNF) plays vitally important roles in neural development and plasticity in both health and disease. Recent studies using mutant mice to selectively manipulate BDNF signalling in desired cell types, in combination with animal models of demyelinating disease, have demonstrated that BDNF not only potentiates normal central nervous system myelination in development but enhances recovery after myelin injury. However, the precise mechanisms by which BDNF enhances myelination in development and repair are unclear. Here, we review some of the recent progress made in understanding the influence BDNF exerts upon the myelinating process during development and after injury, and discuss the cellular and molecular mechanisms underlying its effects. In doing so, we raise new questions for future research.

scholarly journals Emerging chikungunya virus variants at the E1-E1 inter-glycoprotein spike interface impact virus attachment and Inflammation

2021 ◽  
Author(s):  
Margarita Rangel ◽  
Nicole McAllister ◽  
Kristen Dancel-Manning ◽  
Maria G Noval ◽  
Laurie Silva ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Chikungunya Virus ◽  
Molecular Mechanisms ◽  
Cell Attachment ◽  
Host Cells ◽  
Virus Attachment ◽  
Host Membrane ◽  
Structural Impacts ◽  
Host Evolution

Chikungunya virus (CHIKV) is a re-emerging arthropod-borne alphavirus and a serious threat to human health. Therefore, efforts toward elucidating how this virus causes disease and the molecular mechanisms underlying steps of the viral replication cycle are crucial. Using an in vivo transmission system that allows intra-host evolution, we identified an emerging CHIKV variant carrying a mutation in the E1 glycoprotein (V156A) in the serum of mice and saliva of mosquitoes. E1 V156A has since emerged in humans during an outbreak in Brazil, co-occurring with a second mutation, E1 K211T, suggesting an important role for these residues in CHIKV biology. Given the emergence of these variants, we hypothesized that they function to promote CHIKV infectivity and subsequent disease. Here, we show that E1 V156A and E1 K211T modulate virus attachment and fusion and impact binding to heparin, a homolog of heparan sulfate, a key entry factor on host cells. These variants also exhibit differential neutralization by anti-glycoprotein monoclonal antibodies, suggesting structural impacts on the particle that may be responsible for altered interactions at the host membrane. Finally, E1 V156A and E1 K211T exhibit increased titers in an adult arthritic mouse model and induce increased foot-swelling at the site of injection. Taken together, this work has revealed new roles for E1 where discrete regions of the glycoprotein are able to modulate cell attachment and swelling within the host.

scholarly journals Vector competence of Aedes aegypti and screening for differentially expressed microRNAs exposed to Zika virus

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chunling Zhu ◽  
Yuting Jiang ◽  
Qianghui Zhang ◽  
Jian Gao ◽  
Chaojie Li ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Aedes Aegypti ◽  
Mirna Expression ◽  
Zika Virus ◽  
Molecular Mechanisms ◽  
Transmission Rate ◽  
Vector Competence ◽  
Expression Profiles ◽  
Future Research ◽  
Mirna Expression Profiles

Abstract Background Zika virus (ZIKV) is transmitted to humans primarily by Aedes aegypti. Previous studies on Ae. aegypti from Jiegao (JG) and Mengding (MD) in Yunnan province, China have shown that these mosquitoes are able to transmit ZIKV to their offspring through vertical transmission, indicating that these two Ae. aegypti strains pose a potential risk for ZIKV transmission. However, the vector competence of these two Ae. aegypti strains to ZIKV has not been evaluated and the molecular mechanisms influencing vector competence are still unclear. Methods Aedes aegypti mosquitoes from JG and MD were orally infected with ZIKV, and the infection rate (IR), dissemination rate (DR), transmission rate (TR) and transmission efficiency (TE) of these two mosquito strains were explored to evaluate their vector competence to ZIKV. On 2, 4 and 6 days post-infection (dpi), the small RNA profiles between ZIKV-infected and non-infected Ae. aegypti midgut and salivary gland tissues were compared to gain insights into the molecular interactions between ZIKV and Ae. aegypti. Results There were no significant differences in the IR, DR, TR and TE between the two Ae. aegypti strains (P > 0.05). However, ZIKV RNA appeared 2 days earlier in saliva of the JG strain, which indicated a higher competence of the JG strain to transmit ZIKV. Significant differences in the microRNA (miRNA) expression profiles between ZIKV-infected and non-infected Ae. aegypti were found in the 2-dpi libraries of both the midgut and salivary gland tissues from the two strains. In addition, 27 and 74 miRNAs (|log2 fold change| > 2) were selected from the miRNA expression profiles of ZIKV-infected and non-infected midgut and salivary gland tissues from the JG and MD strains, respectively. Conclusions Our results provide novel insights into the ZIKV–mosquito interactions and build a foundation for future research on how miRNAs regulate the vector competence of mosquitoes to this arbovirus. Graphical abstract

scholarly journals Cryptosporidium parvum gp40/15 Is Associated with the Parasitophorous Vacuole Membrane and Is a Potential Vaccine Target

2020 ◽  
Vol 8 (3) ◽  
pp. 363
Author(s):  
Zhaohui Cui ◽  
Luyang Wang ◽  
Yuexin Wang ◽  
Juan Li ◽  
Rongjun Wang ◽  
...  
Keyword(s):  
Cryptosporidium Parvum ◽  
Molecular Mechanisms ◽  
Protein Localization ◽  
Parasitophorous Vacuole ◽  
Expression Patterns ◽  
Surface Proteins ◽  
Host Cells ◽  
Parasitophorous Vacuole Membrane ◽  
Vacuole Membrane

Cryptosporidium parvum is a zoonotic intracellular protozoan responsible for the diarrheal illness cryptosporidiosis in humans and animals. Although a number of zoite surface proteins are known to be expressed during, and believed to be involved in, attachment and invasion of host cells, the molecular mechanisms by which C. parvum invades the host epithelial cells are not well understood. In the present study, we investigated the gene expression patterns, protein localization in developmental stages in culture, and in vitro neutralization characteristics of Cpgp40/15 and Cpgp40. Indirect immunofluorescence assay showed that Cpgp40/15 is associated with the parasitophorous vacuole membrane (PVM) during intracellular development. Both anti-gp40/15 and anti-gp40 antibodies demonstrated the ability to neutralize C. parvum infection in vitro. Further studies are needed to fully understand the specific role and functional mechanism of Cpgp40/15 (or gp40/15 complex) in the invasion of the host or in the PVM and to determine the feasibility of gp40/15 as a vaccine candidate for cryptosporidiosis in vivo.

scholarly journals Covalent host-targeting by thioester domains of Gram-positive pathogens

2014 ◽  
Vol 70 (a1) ◽  
pp. C848-C848
Author(s):  
Miriam Walden ◽  
John Edwards ◽  
Aleksandra Dziewulska ◽  
Uli Schwarz-Linek ◽  
Mark Banfield
Keyword(s):  
Cell Surface ◽  
Host Cell ◽  
Molecular Mechanisms ◽  
Cell Attachment ◽  
Surface Proteins ◽  
Host Cells ◽  
Covalent Attachment ◽  
Gram Positive ◽  
Covalent Bonds ◽  
Isopeptide Bonds

Gram-positive pathogens are a major concern to global health, with increasing resistance to antimicrobials and the lack of preventative therapeutics. Understanding how these bacteria interact with host cells is vital for the development of novel strategies to combat disease. One of the most crucial steps in infection is adhesion to the host cell. The discovery of complex cell-surface associated proteins, such as pili, has advanced our knowledge of this interaction, however the precise molecular mechanisms underlying this process remain unclear. Structural studies of pili revealed the presence of highly unusual intramolecular covalent bonds between amino acid side chains. These include isopeptide bonds between Lys and Asp/Asn residues, conferring mechanical strength, thermal stability and resistance to proteases [1,2]. In Streptococcus pyogenes pili, the adhesin Spy0125 (or Cpa) interacts with the host cell. It comprises three domains, two of which contain stabilising isopeptide bonds [2,3]. Intriguingly, the third domain contains an extremely rare thioester bond, between a Cys and a Gln residue. A Cys to Ala mutation results in a 75% reduction in adhesion, suggesting that this internal linkage may mediate direct attachment [3]. We have now discovered putative thioester domains (TEDs) in cell-surface proteins of several clinically important pathogens. The only other example of an internal thioester is found in complement proteins, where the reactive bond enables the formation of covalent attachment to pathogens. The presence of these bonds in bacterial proteins suggests the possibility of an as-yet uncharacterised, conserved mechanism of covalent host cell attachment. For a selection of pathogens, we have used mass spectrometry and crystallography to confirm the presence of the covalent link between the Cys and Gln residues within the TEDs. Furthermore, we have identified putative host cell targets of TEDs and confirmed covalent linkages between the TED and the target.

scholarly journals Animal Coronaviruses Induced Apoptosis

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 185
Author(s):  
Katerina Gioti ◽  
Christine Kottaridi ◽  
Chrysa Voyiatzaki ◽  
Dimitrios Chaniotis ◽  
Theodoros Rampias ◽  
...  
Keyword(s):  
Cell Death ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Adaptive Immune Response ◽  
Cell Types ◽  
Host Cells ◽  
Future Research ◽  
Molecular Aspects ◽  
Apoptotic Pathways ◽  
Induced Apoptosis

Apoptosis is a form of programmed death that has also been observed in cells infected by several viruses. It is considered one of the most critical innate immune mechanisms that limits pathogen proliferation and propagation before the initiation of the adaptive immune response. Recent studies investigating the cellular responses to SARS-CoV and SARS-CoV-2 infection have revealed that coronaviruses can alter cellular homeostasis and promote cell death, providing evidence that the modulation of apoptotic pathways is important for viral replication and propagation. Despite the genetic diversity among different coronavirus clades and the infection of different cell types and several hosts, research studies in animal coronaviruses indicate that apoptosis in host cells is induced by common molecular mechanisms and apoptotic pathways. We summarize and critically review current knowledge on the molecular aspects of cell-death regulation during animal coronaviruses infection and the viral–host interactions to this process. Future research is expected to lead to a better understanding of the regulation of cell death during coronavirus infection. Moreover, investigating the role of viral proteins in this process will help us to identify novel antiviral targets related to apoptotic signaling pathways.

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