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Directed molecular evolution improves the immunogenicity and protective efficacy of a Venezuelan equine encephalitis virus DNA vaccine.

We employed directed molecular evolution to improve the cross-reactivity and immunogenicity of the Venezuelan equine encephalitis virus (VEE … . Our results indicate that it is possible to improve the immunogenicity and protective efficacy of alphavirus DNA vaccines using directed molecular evolution.

Chikungunya virus: global epidemiology, transmission dynamics, and emerging challenges for public health.

During the last twenty years, Chikungunya virus (CHIKV), an arthropod-borne alphavirus, has resurged globally and emerged as an important public health concern. Driven by viral adaptive mutations, rapid urbanization, climate change, and the global expansion of Aedes mosquito habitats, CHIKV has continuously expanded its geographic distribution and triggered recurrent outbreaks across multiple continents. In this review, we comprehensively synthesize recent progress in virology, epidemiology, vector biology, diagnostic innovations, and vaccine research, emphasizing the integrated mechanisms tha…

Viral Kinetics During Acute Chikungunya Virus Infection: Insights Into Potential Role of Monoclonal Antibodies in Viral Clearance and Prophylaxis Using Mathematical Modeling.

Chikungunya virus (CHIKV), an arthritogenic alphavirus, is a significant public health threat in endemic and newly affected regions. This study investigates viral kinetics, immune responses, and the potential of monoclonal antibody (mAb) therapies to mitigate viraemia and transmission during acute CHIKV infection, providing novel insights into early intervention strategies. Using data from 29 patients in Cambodia, serial sampling and viral load quantification revealed that the population-average peak viral load occurred ~1.87 days prior to symptom onset. Children demonstrated higher peak viral…

A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.

Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious monon … levant immunogens for vaccine development. Here, we developed and optimized the delivery of several alphavirus-derived replicon RNA (repRNA) vaccine candidates encoding gH/gL, gH/gL/gp42 or gp350 delivered by a cationic nanocarrier termed LION™. The lead candidate, encoding full-length gH/gL, elicited high titers of neutralizing antibodies that persisted for …

Live-attenuated CHIKV vaccine with rearranged genome replicates in vitro and induces immune response in mice.

Chikungunya fever virus (CHIKV) is a mosquito-borne alphavirus that causes wide-spread human infections and epidemics in Asia, Africa and recently, in the Americas. CHIKV is considered a priority pathogen by CEPI and WHO. Despite recent approval of a live-attenuated CHIKV vaccine, development of additional vaccines is warranted due to the worldwide outbreaks of CHIKV. Previously, we developed immunization DNA (iDNA) plasmid capable of launching live-attenuated CHIKV vaccine in vivo. Here we report the use of CHIKV iDNA plasmid to prepare a novel, live-attenuated CHIKV vaccine V5040 with rearra…

Real-time RT-PCR for Venezuelan equine encephalitis complex, Madariaga, and Eastern equine encephalitis viruses: application in human and mosquito public health surveillance in Panama.

Eastern equine encephalitis virus (EEEV), Madariaga virus (MADV), and Venezuelan equine encephalitis virus complex (VEEV) are New World alphaviruses transmitted by mosquitoes. They cause febrile and sometimes severe neurological diseases in human and equine hosts. Detecting them during the acute phase is hindered by non-specific symptoms and limited diagnostic tools. We designed and clinically assessed real-time reverse transcription polymerase chain reaction assays (rRT-PCRs) for VEEV complex, MADV, and EEEV using whole-genome sequences. Validation involved 15 retrospective serum samples from…

Radicicol Inhibits Chikungunya Virus Replication by Targeting Nonstructural Protein 2.

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes a debilitating febrile illness characterized by persistent muscle and joint pain. The widespread distribution of transmission-competent vectors, Aedes species mosquitoes, indicates the potential risk of large-scale epidemics with high attack rates that can severely impact public health globally. Despite this, currently, there are no antivirals available for the treatment of CHIKV infections. Thus, we aimed to identify potential drug candidates by screening a chemical library using a cytopathic effect-based high-throughput scr…

Ross River Virus Provokes Differentially Expressed MicroRNA and RNA Interference Responses in Aedes aegypti Mosquitoes.

Alphaviruses are globally distributed and predominately transmitted by mosquitoes. Aedes species are common vectors for the clinically important alphaviruses-Chikungunya, Sindbis, and Ross River (RRV) viruses-with Aedes aegypti also being a vector for the flaviviruses dengue, Yellow Fever, and Zika viruses. Ae. aegypti was putatively implicated in the large 1979-1980 South Pacific Islands outbreak of RRV-the leading cause of arboviral disease in Australia today. The RNA interference (RNAi) defense response in mosquitoes involves a number of small RNAs, with their kinetics induced by alphavirus…

Exacerbation of Chikungunya Virus Rheumatic Immunopathology by a High Fiber Diet and Butyrate.

Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus associated with a robust systemic infection and an acute inflammatory rheumatic disease. A high fiber diet has been widely promoted for its ability to ameliorate inflammatory diseases. Fiber is fermented in the gut into short chain fatty acids such as acetate, propionate, and butyrate, which enter the circulation providing systemic anti-inflammatory activities. Herein we show that mice fed a high fiber diet show a clear exacerbation of CHIKV arthropathy, with increased edema and neutrophil infiltrates. RNA-Seq analyses illustrated …

VIGOR extended to annotate genomes for additional 12 different viruses.

A gene prediction program, VIGOR (Viral Genome ORF Reader), was developed at J. Craig Venter Institute in 2010 and has been successfully per … edict genes for 12 viruses: measles virus, mumps virus, rubella virus, respiratory syncytial virus, alphavirus and Venezuelan equine encephalitis virus, norovirus, metapneumovirus, yellow fever virus, Japanese encephalitis virus, parainfluenza virus and Sendai virus. VIGOR accurately detects the complex gene features like ribonucleicacid editing, stop codon …

Detection of RNA from a novel West Nile-like virus and high prevalence of an insect-specific flavivirus in mosquitoes in the Yucatan Peninsula of Mexico.

As part of our ongoing surveillance efforts for West Nile virus (WNV) in the Yucatan Peninsula of Mexico, 96,687 mosquitoes collected from January through December 2007 were assayed by virus isolation in mammalian cells. Three mosquito pools caused cytopathic effect. Two isolates were orthobunyaviruses (Cache Valley virus and Kairi virus) and the identity of the third infectious agent was not determined. A subset of mosquitoes was also tested by reverse transcription-polymerase chain reaction (RT-PCR) using WNV-, flavivirus-, alphavirus-, and orthobunyavirus-specific primers. A total of 7,009 …

[Serological monitoring of arbovirus infections in the estuary of the Kuban River (the 2006-2007 data)].

Solid-phase enzyme immunoassay, neutralization test, and the hemagglutination-inhibition test were used to study the sera from human beings (152 samples), agricultural animals (n = 77), hares (n = 3), and wild birds (n = 69), collected in 2006-2007 in the Kuban River estuary (Temryuk District, Krasnodar Territory). There were specific antibodies against viruses of West Nile (WH), tick-borne encephalitis (TBE) (Flaviviridae, Flavivirus), Sindbis (Togaviridae, Alphavirus), the antigenic complex of California, Batai (Bunyaviridae, Orthobunyavirus), Dhori (Orthomyxoviridae, Thogotovirus). The find…

Ecological studies of enzootic Venezuelan equine encephalitis in north-central Venezuela, 1997-1998.

From 1997-1998, we investigated the possible continuous circulation of epizootic Venezuelan equine encephalitis (VEE) virus suggested by a 1 … sters that displayed no apparent disease. Four other arboviruses belonging to group A (Togaviridae: Alphavirus), two Bunyamwera group (Bunyaviridae), and three Gamboa group (Bunyaviridae) arboviruses were also isolated from hamsters, as well as 8 unidentified viruses. Venezuelan equine encephalitis-specific antibodies were detected in 5 small mammal species: …

Дифференцированная эволюция восточного энцефалитного вирусного популяции в зависимости от типа принимающей клетки.

Цикл трансмиссивных вирусов (арбовирусов) между хостами в двух таксономических таксономических группах, расширяющих позвоночные и беспозвоночных, оба из которых могут по отдельности или в концерте определять ход эволюции арбовируса. В целях разъяснения селективного давления, связанного с воспроизведением вируса в каждой части этого двуххозяевого жизненного цикла, было изучено воздействие типа хост-хозяина на характеристики роста альфавируса Нового мира, восточного энцефалита энцефалита (EEE). Множественные линии родового вируса EEE неоднократно передавались либо через комары, либо через птичьи

Совпадение в аннотации оригинала
Arthropod-borne viruses (arboviruses) cycle between hosts in two widely separated taxonomic groups, vertebrate amplifying hosts and inverteb … f this two-host life cycle, the effects of host type on the growth characteristics of the New World alphavirus, eastern equine encephalitis (EEE) virus, were investigated. Multiple lineages of an ancestral EEE virus stock were repeatedly transferred through either mosquito or avian cells or in alternating passages between these two cell types. When assayed i …

Wolbachia outcompetes mosquito-borne viruses by reprogramming host ATPSβ1-driven ATP metabolism toward symbiotic proliferation.

Wolbachia endosymbionts confer broad-spectrum resistance to mosquito-borne viruses. While the antiviral metabolites in Wolbachia-Aedes have been identified during viral replication, the core metabolic gene underlying this defense across the entire viral infection cycle remains undefined. Here, we demonstrated for the first time that Wolbachia strongly suppressed the emerging alphavirus Venezuelan equine encephalitis virus, extending its known antiviral spectrum. Transcriptomic and functional analyses revealed ATP synthase beta subunit 1 (ATPSβ1) as a key metabolic hub hijacked by both MBV and …

Perspectives on chikungunya vaccinology: from traditional platforms to epitope-driven rational design.

Chikungunya virus (CHIKV) is an arthritogenic alphavirus transmitted mainly by female Aedes aegypti and Aedes albopictus mosquitoes. It causes significant morbidity and persistent arthralgia, with its global spread driven by Aedes vectors and viral lineage diversification. Vaccination remains the most cost-effective prevention strategy, but development is hindered by unpredictable outbreaks, undefined immune correlates of protection, and the variability of immunodominant epitopes. This review analyzes CHIKV's genomic and proteomic features, mechanisms of viral entry and transmission, immune ev…

Retinoic acid is a translation inhibitor against chikungunya virus both in vitro and invivo.

Chikungunya virus (CHIKV), a mosquito-borne alphavirus, causes debilitating febrile and arthritic disease and remains a persistent public health threat in tropical and subtropical regions, with no clinically approved antiviral drugs currently available, which underscores the urgent need for targeted and effective therapeutic interventions. Through high-throughput screening of an FDA-approved compound library, we identified retinoic acid (RA) as a broad-spectrum inhibitor of multiple arboviruses, exhibiting potent activity against CHIKV. Time-of-addition experiments, together with assays on vir…

An experimental multiplex PCR/RT-PCR for detection of the main viruses associated with equine neurological disease.

Viral neurological infections are important causes of morbidity and mortality in horses worldwide. Herein, we describe an end-point multiplex PCR/RT-PCR for simultaneous and differential detection of major equine encephalitis-related agents: rabies virus (RABV), equine herpesvirus type 1 (EHV-1), alphaviruses [Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV), Western equine encephalitis virus (WEEV) and Madariaga virus (MADV)] and flaviviruses [West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Rocio virus (ROCV) and Japanese encephalitis virus (…

Chikungunya-Associated Acute Respiratory Distress Syndrome: A Rare Fatal Case.

Chikungunya fever is an arboviral disease caused by an alphavirus belonging to the family Togaviridae. It commonly presents with fever, severe arthralgia, rash, and myalgia, while severe pulmonary involvement causing acute respiratory distress syndrome (ARDS) is rare. We report a 62-year-old man with obesity, diabetes mellitus, hypertension, obstructive sleep apnoea, coronary artery disease, and interstitial lung disease, who presented with high-grade fever, severe arthralgia, facial puffiness, and rapidly progressive dyspnoea, following recent travel to Lucknow, India. On admission, he had se…

Discovery and development of labdane-oxindole hybrids as small-molecule inhibitors against chikungunya virus infection.

Chikungunya virus (CHIKV) infection, a febrile illness caused by a mosquito-transmitted alphavirus, has afflicted millions of people worldwide. There is currently no approved effective antiviral treatment for CHIKV infection. In this study, we report a new class of small-molecule CHIKV inhibitors, the oxindole-labdanes, that potently block the replication of CHIKV with good selectivity. Andrographolide, a previously reported inhibitor of CHIKV infection, was used as the lead compound for our initial structure-activity relationship (SAR) study. From a focused library of 72 andrographolide analo…