Spatiotemporal Environmental Drivers of Eastern Equine Encephalitis Virus in Central Florida: Towards a Predictive Model for a Lethal Disease.

Eastern equine encephalitis virus (EEEV) is a mosquito-borne virus that affects humans and horses, with a high case fatality rate in both species. The virus can be transmitted by several mosquito species and maintained in multiple reservoir hosts, making EEEV dynamics difficult to anticipate. In this study, we identified spatial and temporal factors that precede EEEV detection using sentinel chicken surveillance data from Orange County, Florida, from 2003 to 2017.

Arboviral Equine Encephalitides.

A number of viruses transmitted by biological vectors or through direct contact, air, or ingestion cause neurologic disease in equids. Of interest are viruses of the Togaviridae, Flaviviridae, Rhabdoviridae, Herpesviridae, Bornaviridae, and Bunyaviridae families. Many are classified as arboviruses because they use arthropod vectors, whereas others are transmitted directly via ingestion, inhalation, or integument damage.

PCP consensus protein/peptide alphavirus antigens stimulate broad spectrum neutralizing antibodies.

Vaccines based on proteins and peptides may be safer and if calculated based on many sequences, more broad-spectrum than those designed based on single strains. Physicochemical Property Consensus (PCP) alphavirus (AV) antigens from the B-domain of the E2 envelope protein were designed, synthesized recombinantly and shown to be immunogenic (i.e.

Cryo-EM structures of alphavirus conformational intermediates in low pH-triggered prefusion states.

Alphaviruses can cause severe human arthritis and encephalitis. During virus infection, structural changes of viral glycoproteins in the acidified endosome trigger virus-host membrane fusion for delivery of the capsid core and RNA genome into the cytosol to initiate virus translation and replication. However, mechanisms by which E1 and E2 glycoproteins rearrange in this process remain unknown.

North American Arboviruses and White-Tailed Deer (): Associated Diseases and Role in Transmission.

Arboviral disease is of increasing concern to human and animal health professionals as emerging and re-emerging arboviruses are more frequently recognized. Wildlife species are known to play a role in the transmission and maintenance of arboviruses and infections can result in morbidity and mortality in wildlife hosts. In this review, we detail existing evidence of white-tailed deer () as an important host to a diverse collection of arboviruses and evaluate the utility of this species as a resource to better understand the epidemiology of related viral diseases.

EGR1 Upregulation during Encephalitic Viral Infections Contributes to Inflammation and Cell Death.

Early growth response 1 (EGR1) is an immediate early gene and transcription factor previously found to be significantly upregulated in human astrocytoma cells infected with Venezuelan equine encephalitis virus (VEEV). The loss of EGR1 resulted in decreased cell death but had no significant impact on viral replication. Here, we extend these studies to determine the impacts of EGR1 on gene expression following viral infection.

Safety and immunogenicity of a trivalent virus-like particle vaccine against western, eastern, and Venezuelan equine encephalitis viruses: a phase 1, open-label, dose-escalation, randomised clinical trial.

Background: Western (WEEV), eastern (EEEV), and Venezuelan (VEEV) equine encephalitis viruses are mosquito-borne pathogens classified as potential biological warfare agents for which there are currently no approved human vaccines or therapies. We aimed to evaluate the safety, tolerability, and immunogenicity of an investigational trivalent virus-like particle (VLP) vaccine, western, eastern, and Venezuelan equine encephalitis (WEVEE) VLP, composed of WEEV, EEEV, and VEEV VLPs.

Methods: The WEVEE VLP vaccine was evaluated in a phase 1, randomised, open-label, dose-escalation trial at the Hope Clinic of the Emory Vaccine Center at Emory University, Atlanta, GA, USA.

Eastern equine encephalitis virus rapidly infects and disseminates in the brain and spinal cord of cynomolgus macaques following aerosol challenge.

Eastern equine encephalitis virus (EEEV) is mosquito-borne virus that produces fatal encephalitis in humans. We recently conducted a first of its kind study to investigate EEEV clinical disease course following aerosol challenge in a cynomolgus macaque model utilizing the state-of-the-art telemetry to measure critical physiological parameters. Here, we report the results of a comprehensive pathology study of NHP tissues collected at euthanasia to gain insights into EEEV pathogenesis.

West Nile Virus and Other Domestic Nationally Notifiable Arboviral Diseases - United States, 2020.

Arthropod-borne viruses (arboviruses) are transmitted to humans primarily through the bite of infected mosquitoes and ticks. West Nile virus (WNV), mainly transmitted by Culex species mosquitos, is the leading cause of domestically acquired arboviral disease in the United States (1). Other arboviruses cause sporadic cases of disease and occasional outbreaks.

Piperazinobenzodiazepinones: New Encephalitic Alphavirus Inhibitors via Ring Expansion of 2-Dichloromethylquinazolinones.

Venezuelan and eastern equine encephalitis viruses are disease-causing, neuropathic pathogens with no approved treatment options in humans. While expanding the pharmacophoric model of antialphaviral amidines prepared via a quinazolinone rearrangement, we discovered that diamine-treated, 2-dihalomethylquinolinones unexpectedly afforded ring-expanded piperazine-fused benzodiazepinones. Notably, this new chemotype (19 examples) showed potent, submicromolar inhibition of virus-induced cell death, >7-log reduction of viral yield, and tractable structure-activity relationships across both viruses.

West Nile and Usutu virus seroprevalence in Hungary: A nationwide serosurvey among blood donors in 2019.

In Hungary, West Nile virus (WNV) has been responsible for 459 laboratory confirmed human cases between 2004 and 2019, while the first human Usutu virus (USUV) infection was confirmed only in 2018. A comprehensive serosurvey was conducted among blood donors to assess the WNV and USUV seroprevalence in 2019, one year after the largest European WNV epidemic. Altogether, 3005 plasma samples were collected and screened for WNV and USUV specific Immunoglobulin G (IgG) antibodies by Enzyme-Linked Immunosorbent Assay (ELISA).

Structure of SNX9 SH3 in complex with a viral ligand reveals the molecular basis of its unique specificity for alanine-containing class I SH3 motifs.

Class I SH3 domain-binding motifs generally comply with the consensus sequence [R/K]xØPxxP, the hydrophobic residue Ø being proline or leucine. We have studied the unusual Ø = Ala-specificity of SNX9 SH3 by determining its complex structure with a peptide present in eastern equine encephalitis virus (EEEV) nsP3. The structure revealed the length and composition of the n-Src loop as important factors determining specificity.

Predicting eastern equine encephalitis spread in North America: An ecological study.

Eastern equine encephalitis (EEE) is a rare but lethal mosquito-borne zoonotic disease. Recent years have seen incursion into new areas of the USA, and in 2019 the highest number of human cases in decades. Due to the low detection rate of EEE, previous studies were unable to quantify large-scale and recent EEE ecological dynamics.

Development and Validation of a Colorimetric Reverse Transcriptase Loop-Mediated Isothermal Amplification Assay for Detection of Eastern Equine Encephalitis Virus in Mosquitoes.

Eastern equine encephalitis virus (EEEV) is a highly pathogenic alphavirus that causes periodic outbreaks in the eastern USA. Mosquito abatement programs are faced with various challenges with surveillance and control of EEEV and other mosquito-borne illnesses. Environmental sampling of mosquito populations can be technically complex.

West Nile Virus and Eastern Equine Encephalitis Virus High Probability Habitat Identification for the Selection of Sentinel Chicken Surveillance Sites in Florida.

To mitigate the effects of West Nile virus (WNV) and eastern equine encephalitis virus (EEEV), the state of Florida conducts a serosurveillance program that uses sentinel chickens operated by mosquito control programs at numerous locations throughout the state. Coop locations were initially established to detect St. Louis encephalitis virus (SLEV), and coop placement was determined based on the location of human SLEV infections that occurred between 1959 and 1977.

Inactivation of Venezuelan Equine Encephalitis Virus Genome Using Two Methods.

Venezuelan equine encephalitis virus (VEEV) is an Alphavirus in the Togaviridae family of positive-strand RNA viruses. The viral genome of positive-strand RNA viruses is infectious, as it produces infectious virus upon introduction into a cell. VEEV is a select agent and samples containing viral RNA are subject to additional regulations due to their infectious nature.

Alphavirus Identification in Neotropical Bats.

Alphaviruses () are arthropod-borne viruses responsible for several emerging diseases, maintained in nature through transmission between hematophagous arthropod vectors and susceptible vertebrate hosts. Although bats harbor many species of viruses, their role as reservoir hosts in emergent zoonoses has been verified only in a few cases. With bats being the second most diverse order of mammals, their implication in arbovirus infections needs to be elucidated.

Seroepidemiological Survey of West Nile Virus Infections in Horses from Berlin/Brandenburg and North Rhine-Westphalia, Germany.

Following the introduction of the West Nile virus (WNV) into eastern Germany in 2018, increasing infections have been diagnosed in birds, equines, and humans over time, while the spread of WNV into western Germany remained unclear. We screened 437 equine sera from 2018 to 2020, excluding vaccinated horses, collected from convenience sampled patients in the eastern and western parts of Germany, for WNV-specific antibodies (ELISAs followed by virus/specific neutralization tests) and genomes (RT-qPCRs). Clinical presentations, final diagnoses, and demographic data were also recorded.

Glycosaminoglycan binding by arboviruses: a cautionary tale.

Arboviruses are medically important arthropod-borne viruses that cause a range of diseases in humans from febrile illness to arthritis, encephalitis and hemorrhagic fever. Given their transmission cycles, these viruses face the challenge of replicating in evolutionarily divergent organisms that can include ticks, flies, mosquitoes, birds, rodents, reptiles and primates. Furthermore, their cell attachment receptor utilization may be affected by the opposing needs for generating high and sustained serum viremia in vertebrates such that virus particles are efficiently collected during a hematophagous arthropod blood meal but they must also bind sufficiently to cellular structures on divergent organisms such that productive infection can be initiated and viremia generated.

VLDLR and ApoER2 are receptors for multiple alphaviruses.

Alphaviruses, like many other arthropod-borne viruses, infect vertebrate species and insect vectors separated by hundreds of millions of years of evolutionary history. Entry into evolutionarily divergent host cells can be accomplished by recognition of different cellular receptors in different species, or by binding to receptors that are highly conserved across species. Although multiple alphavirus receptors have been described, most are not shared among vertebrate and invertebrate hosts.

Magnetic resonance imaging, clinicopathologic findings, and clinical progression of a puppy with confirmed Eastern equine encephalitis virus.

A 5-month-old puppy was evaluated for rapidly progressive neurologic signs and pyrexia. Magnetic resonance imaging showed multifocal meningoencephalitis with transtentorial and foramen magnum herniation. A cerebrospinal fluid tap revealed highly cellular fluid, and the puppy was euthanized.

Eastern Equine Encephalitis: Case Series in Southern New England and Review of the Literature.

Purpose Of Review: To describe the clinical presentation, diagnosis, management, and outcomes of 4 confirmed Eastern equine encephalitis (EEE) cases and a review of the literature.

Recent Findings: There was a sharp rise in the number of EEE cases in the United States in 2019, with 38 confirmed cases and 15 deaths. Our institution cared for 10% of patients with neuroinvasive EEE nationwide.

Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV.

The three encephalitic alphaviruses, namely, the Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV), are classified by the Centers for Disease Control and Prevention (CDC) as biothreat agents. Currently, no licensed medical countermeasures (MCMs) against these viruses are available for humans. Neutralizing antibodies (NAbs) are fast-acting and highly effective MCMs for use in both pre- and post-exposure settings against biothreat agents.