Effects of Infectious Virus Dose and Bloodmeal Delivery Method on Susceptibility ofAedes aegyptiandAedes albopictusto Chikungunya Virus

Cleavage of the alphavirus precursor glycoprotein p62 into the E2 and E3 glycoproteins before assembly with the nucleocapsid is the key to producing fusion-competent mature spikes on alphaviruses. Here we present a cryo-EM, 6.8-Å resolution structure of an “immature” Chikungunya virus in which the cleavage site has been mutated to inhibit proteolysis. The spikes in the immature virus have a larger radius and are less compact than in the mature virus. Furthermore, domains B on the E2 glycoproteins have less freedom of movement in the immature virus, keeping the fusion loops protected under domain B. In addition, the nucleocapsid of the immature virus is more compact than in the mature virus, protecting a conserved ribosome-binding site in the capsid protein from exposure. These differences suggest that the posttranslational processing of the spikes and nucleocapsid is necessary to produce infectious virus.

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Identification of Chikungunya virus nucleocapsid core assembly modulators

10.1101/774943 ◽

2019 ◽

Author(s):

Sara E. Jones-Burrage ◽

Zhenning Tan ◽

Lichun Li ◽

Adam Zlotnick ◽

Suchetana Mukhopadhyay

Keyword(s):

Nucleic Acid ◽

Capsid Protein ◽

Chikungunya Virus ◽

Infectious Virus ◽

Virus Transmission ◽

Virus Production ◽

List Type ◽

Dependent Manner ◽

Particle Assembly

Abstract:The alphavirus Chikungunya virus is transmitted to humans via infected mosquitos. Most infected humans experience symptoms which can range from short-term fatigue and fever to debilitating arthritis that can last for months or years. Some patients relapse and experience symptoms months or years after the initial bout of disease. The capsid protein of Chikungunya virus forms a shell around the viral RNA genome; this structure is called the nucleocapsid core. The core protects the genome during virus transmission and with the correct environmental trigger, this proteinaceous shell dissociates and releases the viral genome to initiate infection. We hypothesized that targeting compounds to interfere with the nucleocapsid core’s function would constrain virus spread either by inhibiting the release of viral genomes during entry or by reducing the number of infectious virus particles assembled. We implemented a high throughput, in vitro, FRET-based assay to monitor nucleic acid packaging by purified Chikungunya capsid protein as a proxy for nucleocapsid core assembly and disassembly. We screened 10,000 compounds and found 45 that substantially modulated the assembly of core-like particles. A subset of compounds was selected to study their effects in virus-infected vertebrate cells. Our results show that four compounds inhibit infectious virus production by at least 90% in a dose-dependent manner. The most promising inhibitor was tested and found to reduce the amount of nucleocapsid cores inside the cell during Chikungunya virus infection. These compounds could be the foundation for anti-viral therapeutics.HighlightsA FRET-based assay to detect nucleic acid packaging by Chikungunya virus capsid proteinIdentification of small molecules that modulate core-like particle assemblyA subset of compounds that interfere with in vitro assembly also inhibit Chikungunya virus production in cell cultureIdentification of antiviral molecules that may not be identified by assays using reporter virusesPotential starting compounds for developing direct-acting antivirals

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Reimbursement and Telepractice

Perspectives on Telepractice ◽

10.1044/teles3.2.35 ◽

2013 ◽

Vol 3 (2) ◽

pp. 35-40

Author(s):

Carol Dudding

Keyword(s):

Service Delivery ◽

Healthcare Services ◽

Speech Language Pathology ◽

Delivery Method ◽

Quality Healthcare ◽

Service Delivery Models ◽

Private Lives ◽

Language Pathology ◽

Delivery Models

Whether in our professional or private lives, we are all aware of the system wide efforts to provide quality healthcare services while containing the costs. Telemedicine as a method of service delivery has expanded as a result of changes in reimbursement and service delivery models. The growth and sustainability of telehealth within speech-language pathology and audiology, like any other service, depends on the ability to be reimbursed for services provided. Currently, reimbursement for services delivered via telehealth is variable and depends on numerous factors. An understanding of these factors and a willingness to advocate for increased reimbursement can bolster the success of practitioners interested in the telehealth as a service delivery method.

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Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template

Nature ◽

10.1038/news020708-17 ◽

2002 ◽

Keyword(s):

Chemical Synthesis ◽

Infectious Virus ◽

Natural Template

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Analysis of Learners’ Perception on the SPAT Format as a Delivery Method in Mobile Learning

Korean Association for Educational Information and Media ◽

10.15833/kafeiam.22.2.325 ◽

2016 ◽

Vol 22 (2) ◽

pp. 325-349

Author(s):

Yujin Park ◽

Sunyoung Keum ◽

Myungsun Kim ◽

Ilju Rha

Keyword(s):

Mobile Learning ◽

Delivery Method

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Characterization of differentAedes aegyptipopulations in Florida for interfering with chikungunya virus transmission

10.1603/ice.2016.114610 ◽

2016 ◽

Author(s):

Chelsea Smartt

Keyword(s):

Chikungunya Virus ◽

Virus Transmission

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TRANSIENT HYPOGAMMAGLOBULINEMIA OF INFANCY IN FOUR PATIENTS BORN TO MOTHERS INFECTED BY CHIKUNGUNYA VIRUS IN THE LAST TRIMESTER OF PREGNANCY

10.26226/morressier.57bc1758d462b80290b4d3e2 ◽

2016 ◽

Author(s):

Marielly Herrera Maimone

Keyword(s):

Chikungunya Virus

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Silica Sol-Gel Microbead Encapsulation as a Novel Delivery Method for Symbiotic Microbes

10.26434/chemrxiv.13277495.v1 ◽

2020 ◽

Author(s):

Luke Elissiry ◽

Jingwen Sun ◽

Ann M. Hirsch ◽

Chong Liu

Keyword(s):

Plant Growth ◽

Crop Yields ◽

Sol Gel ◽

Plate Count ◽

Similar Amount ◽

Delivery Method ◽

Hormone Production ◽

Promising Alternative ◽

Synthetic Fertilizer ◽

Inorganic Nanomaterials

Synthetic fertilizer is responsible for the greatly increased crop yields that have enabled worldwide industrialization. However, the production and use of such fertilizers are environmentally unfriendly and unsustainable; synthetic fertilizers are produced via non-renewable resources and fertilizer runoff causes groundwater contamination and eutrophication. A promising alternative to synthetic fertilizer is bacterial inoculation. In this process, a symbiotic relationship is formed between a crop and bacteria species that can fix nitrogen, solubilize phosphorus, and stimulate plant hormone production. The bacteria carrier developed here aims to maintain bacteria viability while in storage, protect bacteria while encapsulated, and provide a sustained and controllable bacterial release. This novel bacterial delivery method utilizes inorganic nanomaterials, silica microbeads, to encapsulate symbiotic bacteria. These microbeads, which were produced with aqueous, non-toxic precursors, are sprayed directly onto crop seeds and solidify on the seeds as a resilient silica matrix. The bacterial release from the carrier was found by submerging coated seeds in solution to simulate degradation in soil environments, measuring the number of bacteria released by the plate count technique, and comparing the carrier to seeds coated only in bacteria. The carrier’s effectiveness to enhance plant growth was determined through greenhouse plant assays with alfalfa (<i>Medicago sativa</i>) plants and the nitrogen-fixing <i>Sinorhizobium meliloti</i> Rm1021 strain. When compared to bacteria-only inoculation, the silica microbead carrier exhibited significantly (P < 0.05) increased holding capacity of viable bacteria and increased plant growth by a similar amount, demonstrating the capability of inorganic nanomaterials for microbial delivery. The carrier presented in this work has potential applications for commercial agriculture and presents an opportunity to further pursue more sustainable agricultural practices.

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