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Possible Effects of C-Reactive Protein in the Central Nervous System During Venezuelan Equine Encephalitis Virus Infection.

Venezuelan equine encephalitis virus (VEEV) is an alphavirus vectored by mosquitos. It can cause disease in equines and humans characterised by a febrile illness that may progress into encephalitis. Replication of VEEV in the central nervous system induces activation of glial cells and neurons, compromising the blood-brain barrier (BBB) and inducing a state of neuroinflammation. This inflammation can lead to symptoms such as confusion, seizures, and coma, and sustained inflammation contributes to neurodegeneration. C-reactive protein (CRP) is a biomarker that has previously been associated wit…

Differential restriction of chikungunya virus in primary human cardiac endothelial cells occurs at multiple steps in the viral life cycle.

Arthropod-borne viruses (arboviruses) constitute a significant ongoing public health threat, as the mechanisms of pathogenesis remain incompletely understood. Cardiovascular symptomatology is emerging as an important manifestation of arboviral infection. We have recently studied the cardiac tropism implicated in cardiac infection in mice for the alphavirus chikungunya virus (CHIKV), and we therefore sought to evaluate the cardiac tropism of other emerging alphaviruses and arboviruses. Using human primary cardiac cells, we found that arboviruses from diverse viral families were able to replicat…

Complex antigen presentation pathway for an HLA-A*0201-restricted epitope from Chikungunya 6K protein.

BACKGROUND: The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is critical for clearance of many viral infections. These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells. This specific recognition allows the killing of virus-infected cells. The T cell immune T cell response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe musculoskeletal disorders, has not been fully defined; nonetheless, the importance of HLA class …

Development and validation of an E2 based indirect ELISA for serological detection of porcine Getah virus.

Getah virus (GETV) is an emerging mosquito borne alphavirus that has recently expanded in Chinese swine herds and causes reproductive losses and reduced growth in pigs. The absence of a standardized high throughput serological assay has limited surveillance and hindered accurate assessment of GETV circulation. In this study, we developed and validated an indirect ELISA based on recombinant full length E2 protein for detection of anti-GETV IgG in swine serum. The E2 gene from a circulating strain was expressed in Escherichia coli as inclusion bodies, followed by denaturation, redox refolding, a…

Essential role of the CCL2-CCR2 axis in Mayaro virus-induced disease.

Mayaro virus (MAYV) is an emerging arbovirus member of the Togaviridae family and Alphavirus genus. MAYV infection causes an acute febrile illness accompanied by persistent polyarthralgia and myalgia. Understanding the mechanisms involved in arthritis caused by alphaviruses is necessary to develop specific therapies. In this work, we investigated the role of the CCL2/CCR2 axis in the pathogenesis of MAYV-induced disease. For this, wild-type (WT) C57BL/6J and CCR2-/- mice were infected with MAYV subcutaneously and evaluated for disease development. MAYV infection induced an acute inflammatory d…

Imported Mayaro virus infection in the Netherlands.

A Dutch couple, presenting with persisting arthralgias, temporary fever and rash after a stay in Surinam were diagnosed with Mayaro virus infection. Mayaro virus is a relatively unknown South American Alphavirus responsible for dengue-like clinical features and persisting arthralgias. An important, but probably underappreciated cross-reactivity with other Alphaviruses like Chikungunya virus is present, which may become of clinical importance in the event the various Alphaviruses will have overlapping geographical distributions and in seroprevalence studies.

Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model.

Alzheimer's disease is classified as a progressive disorder resulting from protein misfolding, also known as proteinopathies. Proteinopathie … cible, and well-characterized mouse model for β-amyloidosis, Tg2576, we studied the contribution of alphavirus-induced encephalitis (TC-83 strain of VEEV to model alphavirus encephalitis viruses) on the progression of neurodegenerative pathology. We longitudinally evaluated neurological, neurobehavioral, and cognitive levels, followed by a post-mortem analys …

Identification and molecular docking of novel chikungunya virus NSP4 inhibitory peptides from camel milk proteins.

The chikungunya (CHIK) virus is an arbovirus belonging to the alphavirus (Togaviridae family). Around 85% of infected individuals suffer from symptoms such as high fever and severe joint pain; about 30 to 40% will develop a chronic joint illness. The Nsp4 protease is the most conserved protein in the alphavirus family and serves as an RNA-dependent RNA polymerase (RdRp). Targeting this enzyme might inhibit the CHIKV replication cycle. This work aims to in silico study the CHIKV RdRp inhibitory effect of peptides derived from camel milk protein as antiviral peptides. Various bioinformatics tool…

Phylogenetic and Timescale Analysis of Barmah Forest Virus as Inferred from Genome Sequence Analysis.

Barmah Forest virus (BFV) is a medically important mosquito-borne alphavirus endemic to Australia. Symptomatic disease can be a major cause of morbidity, associated with fever, rash, and debilitating arthralgia. BFV disease is similar to that caused by Ross River virus (RRV), the other major Australian alphavirus. Currently, just four BFV whole-genome sequences are available with no genome-scale phylogeny in existence to robustly characterise genetic diversity. Thirty novel genome sequences were derived for this study, for a final 34-taxon dataset sampled over a 44 year period. Three distinct …

The prophylactic and therapeutic activity of a broadly active ribonucleoside analog in a murine model of intranasal venezuelan equine encephalitis virus infection.

The New World alphaviruses Venezuelan, Eastern, and Western equine encephalitis viruses (VEEV, EEEV and WEEV, respectively) commonly cause a febrile disease that can progress to meningoencephalitis, resulting in significant morbidity and mortality. To address the need for a therapeutic agent for the treatment of Alphavirus infections, we identified and pursued preclinical characterization of a ribonucleoside analog EIDD-1931 (β-D-N4-hydroxycytidine, NHC), which has shown broad activity against alphaviruses in vitro and has a very high genetic barrier for development of resistance. To be truly …

Identification of a specific region in the e1 fusion protein involved in zinc inhibition of semliki forest virus fusion.

The enveloped alphaviruses infect cells via a low-pH-triggered membrane fusion reaction mediated by the viral transmembrane protein E1. During fusion, E1 inserts into the target membrane and refolds to a hairpin-like postfusion conformation in which domain III (DIII) and the juxtamembrane stem pack against a central core trimer. Although zinc has previously been shown to cause a striking block in alphavirus fusion with liposome target membranes, the mechanism of zinc's effect on the E1 fusion protein is not understood. Here we developed a cell culture system to study zinc inhibition of fusion …

Involvement of lipids in different steps of the flavivirus fusion mechanism.

Flavivirus membrane fusion is triggered by acidic pH and mediated by the major envelope protein E. A structurally very similar fusion protein is found in alphaviruses, and these molecules are designated class II viral fusion proteins. In contrast to that of flaviviruses, however, alphavirus fusion has been shown to be absolutely dependent on the presence of cholesterol and sphingomyelin in the target membrane, suggesting significant differences in the fusion protein-membrane interactions that lead to fusion. With the flavivirus tick-borne encephalitis virus (TBEV), we have therefore conducted …

TIM-1 promotes infection with mosquito cell-derived alphaviruses through virion-associated phospholipids.

Human T-cell immunoglobulin and mucin domain 1 (TIM-1) facilitates infection of re-emerging viruses, including alphaviruses, through its phosphatidylserine (PS) binding domain. Although alphaviruses are transmitted to humans via mosquito bite, it is unclear whether mosquito-derived viruses also use TIM-1 to infect human cells. Since viruses acquire their PS-containing envelope from the host cell and insect cell membranes differ in lipid composition from mammalian membranes, we here investigate the role of TIM-1 at the mosquito-mammalian interface. We show that TIM-1 promotes infection with mos…

Разработка и применение обратного транскрипционного анализа полимеразы на основе CRISPR/Cas12a с помощью бокового фильтра потока и флуоресцирующего обнаружения вируса Гета.

Вирус Гетаха (GETV) — переносимый комаром альфавирус, относящийся к зоонотической болезни, в основном заражает скот, особенно свиней и лошадей. В последние годы он вновь появился во многих азиатских странах, создавая потенциальную угрозу для животноводства и здоровья населения. В этом исследовании мы разработали быстрый и чувствительный метод обнаружения GETV, основанный на обратной транскрипции - рекомбиназы полимеразы (RT-RPA) и регулярном стыковке коротких палиндромных повторений (CRISPR)/Cas12a системы в сочетании с боковым фильтром потока (LFD) для визуального считывания. За счет сохранен

Совпадение в аннотации оригинала
Getah virus (GETV), a mosquito-borne alphavirus classified as a zoonotic disease, primarily infects livestock, particularly pigs and horses. In recent years, it has re-emerged in multiple Asian countries, posing a potential threat to animal husbandry and public health. In this study, we developed a rapid and sensitive GETV detection method based on reverse t…

Attenuation of Getah Virus by a Single Amino Acid Substitution at Residue 253 of the E2 Protein that Might Be Part of a New Heparan Sulfate Binding Site on Alphaviruses.

The emergence of new epidemic variants of alphaviruses poses a public health risk. It is associated with adaptive mutations that often cause increased pathogenicity. Getah virus (GETV), a neglected and re-emerging mosquito-borne alphavirus, poses threat to many domestic animals and probably even humans. At present, the underlying mechanisms of GETV pathogenesis are not well defined. We identified a residue in the E2 glycoprotein that is critical for viral adsorption to cultured cells and pathogenesis in vivo. Viruses containing an arginine instead of a lysine at residue 253 displayed enhanced …

Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor Production.

Arthritogenic alphavirus infections often result in debilitating musculoskeletal disorders that affect the joints, muscle, and bone. In order to evaluate the infection profile of primary human skeletal muscle and chondrocyte cells to Ross River virus (RRV) in vitro, cells were infected at a multiplicity of infection (MOI) of 1 over a period of two days. Viral titers were determined by plaque assay and cytokine expression by Bio-Plex® assays using the supernatants harvested. Gene expression studies were conducted using total RNA isolated from cells. Firstly, we show that RRV RNA is detected in …

Status of research and development of vaccines for chikungunya.

Chikungunya virus (CHIKV) is an arthritogenic alphavirus that during the last decade has significantly expanded its geographical range and caused large outbreaks of human disease around the world. Although mortality rates associated with CHIKV outbreaks are low, acute and chronic illnesses caused by CHIKV represent a significant burden of disease largely affecting low and middle income countries. This report summarizes the current status of vaccine development for CHIKV.

Monoclonal Antibodies as Prophylactic and Therapeutic Agents Against Chikungunya Virus.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is responsible for considerable epidemics worldwide and recently emerged in the Americas in 2013. CHIKV may cause long-lasting arthralgia after acute infection. With currently no licensed vaccines or antivirals, the design of effective therapies to prevent or treat CHIKV infection is of utmost importance and will be facilitated by increased understanding of the dynamics of chikungunya. In this article, monoclonal antibodies against CHIKV as viable prophylactic and therapeutic agents will be discussed.

Collection and Processing of Adult Mosquitoes (Diptera: Culicidae) for Molecular Studies of Arbovirus Infection.

The processing of adult mosquitoes collected in the field for studies of natural infection with arboviruses of public health interest (genera: Flavivirus, Alphavirus, Orthobunyavirus) follows the assembly of homogenized mosquito pools and extraction of genetic material using commercial or manual techniques, and the detection of viral RNA by polymerase chain reaction (nested RT-PCR) [11]. This paper describes the procedures for capturing, taxonomic determination, obtaining genetic material, and molecular techniques for detecting alphaviruses.

NAP1L1 and NAP1L4 Binding to Hypervariable Domain of Chikungunya Virus nsP3 Protein Is Bivalent and Requires Phosphorylation.

Chikungunya virus (CHIKV) is one of the most pathogenic members of the Alphavirus genus in the Togaviridae family. Within the last 2 decades, CHIKV has expanded its presence to both hemispheres and is currently circulating in both Old and New Worlds. Despite the severity and persistence of the arthritis it causes in humans, no approved vaccines or therapeutic means have been developed for CHIKV infection. Replication of alphaviruses, including CHIKV, is determined not only by their nonstructural proteins but also by a wide range of host factors, which are indispensable components of viral repl…