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Antiviral Res 2020 Jul 1:104854. Epub 2020 Jul 1.

Virology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD, 21702.

Recent studies highlight that infection with Coxsackievirus B3, Venezuelan equine encephalitis virus (VEEV), Marburg virus, or stimulation using poly I:C (dsRNA), upregulates the signaling adaptor protein MyD88 and impairs the host antiviral type I interferon (IFN) responses. In contrast, MyD88 deficiency (MyD88) increases the type I IFN and survivability of mice implying that MyD88 up regulation limits the type I IFN response. Reasoning that MyD88 inhibition in a virus-like manner may increase type I IFN responses, our studies revealed lipopolysaccharide stimulation of U937 cells or poly I:C stimulation of HEK293-TLR3, THP1 or U87 cells in the presence of a previously reported MyD88 inhibitor (compound 4210) augmented IFN-β and RANTES production. Read More

PLoS One 2020 25;15(6):e0232381. Epub 2020 Jun 25.

Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.

Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. Read More

Trop Med Infect Dis 2020 Jun 22;5(2). Epub 2020 Jun 22.

Retired, Research Program Manager, Wildlife Diseases Program, National Wildlife Research Center, Wildlife Services, USDA, APHIS, Fort Collins, CO 80521, USA.

The epidemic strain of Venezuelan equine encephalitis virus (VEE) 1B invaded south Texas in 1971. The success of the eventual containment and control of the virus invasion was the early recognition and immediate detection, cooperation, coordination, and participation among multiple federal agencies. There were 4739 wild vertebrate animals trapped on a ranch in the area with only 1 VEE virus isolation from a Virgina opossum (Didelphis virginiana). Read More

Viruses 2020 Jun 19;12(6). Epub 2020 Jun 19.

Institute for Human Infections and Immunity, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.

Reporter genes for RNA viruses are well-known to be unstable due to putative RNA recombination events that excise inserted nucleic acids. RNA recombination has been demonstrated to be co-regulated with replication fidelity in alphaviruses, but it is unknown how recombination events at the minority variant level act, which is important for vaccine and trans-gene delivery design. Therefore, we sought to characterize the removal of a reporter gene by a low-fidelity alphavirus mutant over multiple replication cycles. Read More

J Antibiot (Tokyo) 2020 Jun 12. Epub 2020 Jun 12.

Kish International Campus, University of Tehran, Tehran, Iran.

Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly effective against many microorganisms including some viruses. In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in vivo studies over the past 50 years. Read More

EBioMedicine 2020 Jun 5;56:102819. Epub 2020 Jun 5.

Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China; Drug Discovery Center for Infectious Disease, Nankai University, Tianjin 300350, People's Republic of China. Electronic address:

Background: Live attenuated vaccines (LAVs) can mimic natural infection and have advantages to stimulate a robust and sustained immune response as well as to confer long-term protection. However, safety concerns is one of the major obstacles for LAVs development. In an effort to achieve the optimal balance between immunogenicity and safety, researchers currently have taken different strategies for the development of LAVs. Read More

J Control Release 2020 Jun 5;324:644-656. Epub 2020 Jun 5.

Chemical Biological and Radiological Division, Dstl Porton Down, Salisbury SP4 0JQ, UK. Electronic address:

The field of brain drug delivery faces many challenges that hinder development and testing of novel therapies for clinically important central nervous system disorders. Chief among them is how to deliver large biologics across the highly restrictive blood-brain barrier. Non-ionic surfactant vesicles (NISV) have long been used as a drug delivery platform for cutaneous applications and have benefits over comparable liposomes in terms of greater stability, lower cost and suitability for large scale production. Read More

Vaccines (Basel) 2020 Jun 3;8(2). Epub 2020 Jun 3.

Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 505, USA.

Vaccinations are a crucial intervention in combating infectious diseases. The three neurotropic Alphaviruses, Eastern (EEEV), Venezuelan (VEEV), and Western (WEEV) equine encephalitis viruses, are pathogens of interest for animal health, public health, and biological defense. In both equines and humans, these viruses can cause febrile illness that may progress to encephalitis. Read More

Ann Clin Microbiol Antimicrob 2020 May 19;19(1):19. Epub 2020 May 19.

Instituto de Investigaciones Biológicas del Trópico (IIBT), Facultad de Medicina Veterinaria y Zootecnia, Universidad de Córdoba, Montería, Córdoba, Colombia.

The equine encephalitis viruses, Venezuelan (VEEV), East (EEEV) and West (WEEV), belong to the genus alphavirus, family Togaviridae and still represent a threat for human and animal public health in the Americas. In both, these infections are characterized by high viremia, rash, fever, encephalitis and death. VEEV encephalitis is similar, clinically, to other arboviral diseases, such as dengue, Zika or chikungunya. Read More

Viruses 2020 May 15;12(5). Epub 2020 May 15.

Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.

Mutations are incorporated into the genomes of RNA viruses at an optimal frequency and altering this precise frequency has been proposed as a strategy to create live-attenuated vaccines. However, determining the effect of specific mutations that alter fidelity has been difficult because of the rapid selection of the virus population during replication. By deleting residues of the structural polyprotein PE2 cleavage site, E3D56-59, in Venezuelan equine encephalitis virus (VEEV) TC-83 vaccine strain, non-infectious virus particles were used to assess the effect of single mutations on mutation frequency without the interference of selection that results from multiple replication cycles. Read More

Arch Virol 2020 Jul 16;165(7):1715-1717. Epub 2020 May 16.

Virology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD, 21702, USA.

Venezuelan equine encephalitis virus (VEEV) is an important pathogen of medical and veterinary importance in the Americas. In this report, we present the complete genome sequences of five VEEV isolates obtained from pools of Culex (Melanoconion) gnomatos (4) or Culex (Melanoconion) pedroi (1) from Iquitos, Peru. Genetic and phylogenetic analyses showed that all five isolates grouped within the VEEV complex sister to VEEV IIIC and are members of subtype IIID. Read More

Vet World 2020 Mar 16;13(3):495-501. Epub 2020 Mar 16.

Center for Virological Research, University of Sao Paulo, Riberao Preto, Brazil.

Background And Aim: Venezuelan equine encephalitis virus (VEEV) is an alphavirus that causes encephalitis with a high impact on public health in Latin America. However, only in Guatemala, Trinidad and Tobago, and Mexico have found antibodies in VEEV in bats, using immunohistochemistry, the sensitivity and specificity are improved; thus, it is better for demonstrating natural infection in bats as potential hosts. This study aimed to determine the presence of VEEV in tissues of frugivorous bats. Read More

Mol Ther Methods Clin Dev 2020 Apr 15. Epub 2020 Apr 15.

Headquarters, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.

DNA vaccines expressing codon-optimized Venezuelan equine encephalitis virus (VEEV) and Ebola virus (EBOV) glycoprotein genes provide protective immunity to mice and nonhuman primates when delivered by intramuscular (IM) electroporation (EP). To achieve equivalent protective efficacy in the absence of EP, we evaluated VEEV and EBOV DNA vaccines constructed using minimalized Nanoplasmid expression vectors that are smaller than conventional plasmids used for DNA vaccination. These vectors may also be designed to co-express type I interferon inducing innate immune agonist genes that have an adjuvant effect. Read More

Microb Risk Anal 2019 Aug 5;12:27-43. Epub 2019 Mar 5.

15 Weare Close, Portland, Dorset DT5 1JP, United Kingdom.

Arboviruses such as West Nile virus (WNV), bluetongue virus (BTV), dengue virus (DENV) and chikungunya virus (CHIKV) infect their arthropod vectors over a range of average temperatures depending on the ambient temperature. How the transmission efficiency of an arbovirus (i.e. Read More

PLoS Pathog 2020 03 9;16(3):e1008282. Epub 2020 Mar 9.

National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, United States of America.

Protein phosphorylation plays an important role during the life cycle of many viruses. Venezuelan equine encephalitis virus (VEEV) capsid protein has recently been shown to be phosphorylated at four residues. Here those studies are extended to determine the kinase responsible for phosphorylation and the importance of capsid phosphorylation during the viral life cycle. Read More

Vaccines (Basel) 2020 Mar 2;8(1). Epub 2020 Mar 2.

Center for Predictive Medicine, School of Medicine, University of Louisville, Louisville, KY 40202, USA.

The safety and genetic stability of V4020, a novel Venezuelan Equine Encephalitis Virus (VEEV) vaccine based on the investigational VEEV TC-83 strain, was evaluated in mice. V4020 was generated from infectious DNA, contains a stabilizing mutation in the E2-120 glycoprotein, and includes rearrangement of structural genes. After intracranial inoculation (IC), replication of V4020 was more attenuated than TC-83, as documented by low clinical scores, inflammation, viral load in brain, and earlier viral clearance. Read More

Viruses 2020 Feb 27;12(3). Epub 2020 Feb 27.

Department of Biology, Baylor University, Waco, 76798 TX, USA.

Chikungunya virus (CHIKV) is an alphavirus that causes febrile illness punctuated by severe polyarthralgia. After the emergence of CHIKV in the Western Hemisphere, multiple reports of congenital infections were published that documented neurological complications, cardiac defects, respiratory distress, and miscarriage. The Western Hemisphere is endemic to several alphaviruses, and whether antigenic cross-reactivity can impact the course of infection has not been explored. Read More

Vaccine 2020 Mar 25;38(14):2949-2959. Epub 2020 Feb 25.

Department of Pharmacology and Toxicology, School of Medicine, Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, NIH Regional Bio-containment Laboratory, University of Louisville, KY, USA. Electronic address:

Junin (JUNV) and Machupo (MACV), two mammalian arenaviruses placed on the 2018 WHO watch list, are prevalent in South America causing Argentine and Bolivian hemorrhagic fevers (AHF and BHF), respectively. The live attenuated JUNV vaccine, Candid #1, significantly reduced the incidence of AHF. Vaccination induces neutralizing antibody (nAb) responses which effectively target GP1 (the viral attachment glycoprotein) pocket which accepts the tyrosine residue of the cellular receptor, human transferrin receptor 1 (TfR1). Read More

Vaccine 2020 Apr 19;38(17):3378-3386. Epub 2020 Feb 19.

Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA. Electronic address:

Live-attenuated V4020 vaccine for Venezuelan equine encephalitis virus (VEEV) containing attenuating rearrangement of the virus structural genes was evaluated in a non-human primate model for immunogenicity and protective efficacy against aerosol challenge with wild-type VEEV. The genomic RNA of V4020 vaccine virus was encoded in the pMG4020 plasmid under control of the CMV promoter and contained the capsid gene downstream from the glycoprotein genes. It also included attenuating mutations from the VEE TC83 vaccine, with E2-120Arg substitution genetically engineered to prevent reversion mutations. Read More

Front Vet Sci 2019 28;6:509. Epub 2020 Jan 28.

National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA, United States.

Most of the modern techniques used for identification of viral-induced disease are based on identification of viral antigens and/or nucleic acids in patient's blood. Diagnosis in the field or in remote locations can be challenging and alternatively samples are shipped to diagnostic labs for testing. Shipments must occur under controlled temperature conditions to prevent loss of sample integrity. Read More

mBio 2020 02 11;11(1). Epub 2020 Feb 11.

Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA

Venezuelan and western equine encephalitis viruses (VEEV and WEEV, respectively) invade the central nervous system (CNS) early during infection, via neuronal and hematogenous routes. While viral replication mediates host shutoff, including expression of type I interferons (IFN), few studies have addressed how alphaviruses gain access to the CNS during established infection or the mechanisms of viral crossing at the blood-brain barrier (BBB). Here, we show that hematogenous dissemination of VEEV and WEEV into the CNS occurs via caveolin-1 (Cav-1)-mediated transcytosis (Cav-MT) across an intact BBB, which is impeded by IFN and inhibitors of RhoA GTPase. Read More

PLoS One 2020 7;15(1):e0227058. Epub 2020 Jan 7.

National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA, United States of America.

Nanotrap® (NT) particles are hydrogel microspheres developed for target analyte separation and discovery applications. NT particles consist of cross-linked N-isopropylacrylamide (NIPAm) copolymers that are functionalized with a variety of chemical affinity baits to enable broad-spectrum collection and retention of target proteins, nucleic acids, and pathogens. NT particles have been previously shown to capture and enrich arboviruses including Rift Valley fever and Venezuelan equine encephalitis viruses. Read More

Viruses 2019 12 12;11(12). Epub 2019 Dec 12.

National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA.

Venezuelan equine encephalitis virus (VEEV) is a category B select agent pathogen that can be aerosolized. Infections in murine models and humans can advance to an encephalitic phenotype which may result in long-term neurological complications or death. No specific FDA-approved treatments or vaccines are available for the treatment or prevention of VEEV infection. Read More

Antiviral Res 2020 02 6;174:104674. Epub 2019 Dec 6.

Department of Microbiology and Immunology, University of Louisville, 505 South Hancock St, Room 642 C, Louisville, KY, USA; Center of Predictive Medicine, University of Louisville, 505 South Hancock St, Room 617, Louisville, KY, USA. Electronic address:

Venezuelan equine encephalitis virus (VEEV) is an alphavirus that is endemic to the Americas. VEEV outbreaks occur periodically and cause encephalitis in both humans and equids. There are currently no therapeutics or vaccines for treatment of VEEV in humans. Read More

PLoS Pathog 2019 12 2;15(12):e1008157. Epub 2019 Dec 2.

Virology Division, US Army Medical Research Institute of Infectious Disease, Fort Detrick, Maryland, United States of America.

There are no FDA licensed vaccines or therapeutics for Venezuelan equine encephalitis virus (VEEV) which causes a debilitating acute febrile illness in humans that can progress to encephalitis. Previous studies demonstrated that murine and macaque monoclonal antibodies (mAbs) provide prophylactic and therapeutic efficacy against VEEV peripheral and aerosol challenge in mice. Additionally, humanized versions of two neutralizing mAbs specific for the E2 glycoprotein, 1A3B-7 and 1A4A-1, administered singly protected mice against aerosolized VEEV. Read More

J Virol Methods 2020 Mar 28;277:113792. Epub 2019 Nov 28.

Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA. Electronic address:

The challenges associated with operating electron microscopes (EM) in biosafety level 3 and 4 containment facilities have slowed progress of cryo-EM studies of high consequence viruses. We address this gap in a case study of Venezuelan Equine Encephalitis Virus (VEEV) strain TC-83. Chemical inactivation of viruses may physically distort structure, and hence to verify retention of native structure, we selected VEEV strain TC-83 to develop this methodology as this virus has a 4. Read More

J Appl Microbiol 2020 Apr 12;128(4):1050-1059. Epub 2019 Dec 12.

US Environmental Protection Agency, Research Triangle Park, NC, USA.

Aims: The purpose of this study was to evaluate the effects of altered environmental conditions on the persistence of Francisella tularensis bacteria and Venezuelan equine encephalitis virus (VEEV), on two material types.

Methods And Results: Francisella tularensis (F.t. Read More

Am J Trop Med Hyg 2020 01;102(1):195-201

Equipe EA 3593, Ecosystèmes Amazoniens et Pathologie Tropicale, Université de la Guyane, Cayenne, French Guiana.

Tonate virus (TONV) is an arbovirus discovered in 1973 in French Guiana (FG) belonging to the Venezuelan equine encephalitis virus complex, Alphavirus genus. Only few publications and cases have been reported in FG. The objectives of the present study were to describe the clinical picture of TONV and to compare its presentation with that of dengue virus (DENV). Read More

Viruses 2019 11 13;11(11). Epub 2019 Nov 13.

Immunodiagnostic Department, Naval Medical Research Center, 8400 Research Plaza, Fort Detrick, MD 21702, USA.

Traditional pathogenesis studies of alphaviruses involves monitoring survival, viremia, and pathogen dissemination via serial necropsies; however, molecular imaging shifts this paradigm and provides a dynamic assessment of pathogen infection. Positron emission tomography (PET) with PET tracers targeted to study neuroinflammation (,-diethyl-2-[4-phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide, [F]DPA-714), apoptosis (caspase-3 substrate, [F]CP-18), hypoxia (fluormisonidazole, [F]FMISO), blood-brain barrier (BBB) integrity ([F]albumin), and metabolism (fluorodeoxyglucose, [F]FDG) was performed on C3H/HeN mice infected intranasally with 7000 plaque-forming units (PFU) of Venezuelan equine encephalitis virus (VEEV) TC-83. The main findings are as follows: (1) whole-brain [F]DPA-714 and [F]CP-18 uptake increased three-fold demonstrating, neuroinflammation and apoptosis, respectively; (2) [F]albumin uptake increased by 25% across the brain demonstrating an altered BBB; (3) [F]FMISO uptake increased by 50% across the whole brain indicating hypoxic regions; (4) whole-brain [F]FDG uptake was unaffected; (5) [F]DPA-714 uptake in (a) cortex, thalamus, striatum, hypothalamus, and hippocampus increased through day seven and decreased by day 10 post exposure, (b) olfactory bulb increased at day three, peaked day seven, and decreased day 10, and (c) brain stem and cerebellum increased through day 10. Read More

Pathogens 2019 11 16;8(4). Epub 2019 Nov 16.

Center for Vaccine Research, University of Pittsburgh, 3501 Fifth Avenue, Ste. 9052, Pittsburgh, PA 15213, USA.

Eastern (EEEV) and Venezuelan (VEEV) equine encephalitis viruses (EEVs) are related, (+) ssRNA arboviruses that can cause severe, sometimes fatal, encephalitis in humans. EEVs are highly infectious when aerosolized, raising concerns for potential use as biological weapons. No licensed medical countermeasures exist; given the severity/rarity of natural EEV infections, efficacy studies require animal models. Read More

Virology 2020 Jan 31;539:121-128. Epub 2019 Oct 31.

National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA, USA. Electronic address:

Venezuelan equine encephalitis virus (VEEV) is a neurotropic virus that causes significant disease in both humans and equines. Here we characterized the impact of VEEV on signaling pathways regulating cell death in human primary astrocytes. VEEV productively infected primary astrocytes and caused an upregulation of early growth response 1 (EGR1) gene expression at 9 and 18 h post infection. Read More

J Virol 2020 Jan 17;94(3). Epub 2020 Jan 17.

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA

Venezuelan equine encephalitis virus (VEEV) is one of the important human and animal pathogens. It forms replication enzyme complexes (RCs) containing viral nonstructural proteins (nsPs) that mediate the synthesis of virus-specific RNAs. The assembly and associated functions of RC also depend on the presence of a specific set of host proteins. Read More

FEBS Lett 2020 Feb 2;594(4):678-694. Epub 2019 Nov 2.

Department of Biotechnology, Indian Institute of Technology Roorkee, India.

Alphaviruses, including Chikungunya (CHIKV) and Venezuelan equine encephalitis virus (VEEV), are among the leading causes of recurrent epidemics all over the world. Alphaviral nonstructural protein 1 (nsP1) orchestrates the capping of nascent viral RNA via its S-adenosyl methionine-dependent N-7-methyltransferase (MTase) and guanylyltransferase activities. Here, we developed and validated a novel capillary electrophoresis (CE)-based assay for measuring the MTase activity of purified VEEV and CHIKV nsP1. Read More

J Virol 2019 12 26;93(24). Epub 2019 Nov 26.

Center for Vaccine Research, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Alphavirus infection of fibroblastic cell types inhibits host cell translation and transcription, leading to suppression of interferon alpha/beta (IFN-α/β) production. However, the effect of infection upon myeloid cells, which are often the first cells encountered by alphaviruses , is unclear. Previous studies demonstrated an association of systemic IFN-α/β production with myeloid cell infection efficiency. Read More

Am J Trop Med Hyg 2019 12;101(6):1212-1218

Universitat Autònoma de Barcelona, Barcelona, Spain.

Alphaviruses (Togaviridae, ) are arthropod-borne single-stranded RNA pathogens that cause febrile and neurologic disease in much of Latin America. However, many features of Alphavirus epidemiology remain unknown. In 2011, we undertook a cross-sectional study in Nueva Esperanza, an indigenous community in the Peruvian Amazon. Read More

J Virol Methods 2019 12 13;274:113734. Epub 2019 Sep 13.

National Center for Biotechnology, Korgalzhin hwy 13/5, 010000, Astana, Kazakhstan. Electronic address:

Plasmacytoma (myeloma) cells have a large protein expression capacity, although their industrial use is confined to stable expression systems. Vectors derived from genomes of viruses from the genus Alphavirus allow obtaining of high yields of target proteins but their use is limited to transient expression. Little information has been published to date on attempts to combine the myeloma cells as hosts with alphaviruses as expression vectors. Read More

Mol Ther 2019 12 19;27(12):2080-2090. Epub 2019 Aug 19.

Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA, USA; Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Department of Biological Engineering, MIT, Cambridge, MA, USA; Materials Science & Engineering, MIT, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD, USA. Electronic address:

RNA replicons are a promising platform technology for vaccines. To evaluate the potential of lipid nanoparticle-formulated replicons for delivery of HIV immunogens, we designed and tested an alphavirus replicon expressing a self-assembling protein nanoparticle immunogen, the glycoprotein 120 (gp120) germline-targeting engineered outer domain (eOD-GT8) 60-mer. The eOD-GT8 immunogen is a germline-targeting antigen designed to prime human B cells capable of evolving toward VRC01-class broadly neutralizing antibodies. Read More

Antiviral Res 2019 11 5;171:104597. Epub 2019 Sep 5.

Emory Institute for Drug Development (EIDD), Emory University, Atlanta, GA, USA; Drug Innovation Ventures at Emory (DRIVE), Atlanta, GA, USA. Electronic address:

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-N-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 effective as a therapeutic agent for VEEV infection a drug must penetrate the blood brain barrier and arrest virus replication in the brain. Read More

Microbiol Resour Announc 2019 Sep 5;8(36). Epub 2019 Sep 5.

Diagnostic Department, Animal Health National Service (SENASA), Heredia, Costa Rica

The first complete coding sequence of the Venezuelan equine encephalitis virus IE, isolated from a Costa Rican mare with severe encephalitis, was confirmed by histological and viral whole-genome analyses. The isolated virus grouped in the Pacific cluster. Read More

Viruses 2019 08 31;11(9). Epub 2019 Aug 31.

Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND), Joint Project Manager-Medical Countermeasure Systems (JMP-MCS), Joint Vaccine Acquisition Program (JVAP), 1564 Freedman Drive, Fort Detrick, MD 21702, USA.

Licensure of a vaccine to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires use of the U.S. Food and Drug Administration (FDA) Animal Rule to assess vaccine efficacy as human studies are not feasible or ethical. Read More

Pathogens 2019 Aug 15;8(3). Epub 2019 Aug 15.

Indian Institute of Technology Mandi, School of Basic Sciences, VPO Kamand, Himachal Pradesh 175005, India.

Chikungunya virus (CHIKV) infection is one of the major public health concerns, leading thousands of cases every year in rural as well as urban regions of several countries worldwide, few to mention are India, Philippines, Indonesia, and also in American countries. The structural and non-structural proteins of CHIKV are structurally and functionally similar to other alphaviruses such as Sindbis virus, Venezuelan Equine Encephalitis virus. The precursor protein of non-structural proteins is cleaved by proteolytic activity of non-structural protein (nsp2). Read More

ACS Infect Dis 2019 12 11;5(12):2014-2028. Epub 2019 Jul 11.

Chemistry Department, Drug Discovery Division , Southern Research , 2000 Ninth Avenue South , Birmingham , Alabama 35205 , United States.

Alphaviruses are arthropod-transmitted members of the Togaviridae family that can cause severe disease in humans, including debilitating arthralgia and severe neurological complications. Currently, there are no approved vaccines or antiviral therapies directed against the alphaviruses, and care is limited to treating disease symptoms. A phenotypic cell-based high-throughput screen was performed to identify small molecules that inhibit the replication of Venezuelan Equine Encephalitis Virus (VEEV). Read More

J Wildl Dis 2020 01 25;56(1):66-81. Epub 2019 Jun 25.

Field Veterinary Program, Wildlife Conservation Society, 2300 Southern Boulevard, Bronx, New York 10460, USA.

Despite being the most numerous penguin species in South America, exposure of the Magellanic Penguin () to pathogens has not yet been thoroughly assessed. We collected serum from 1,058 Magellanic Penguins at 10 breeding colonies along the entire latitudinal range of this species in Argentina. The work spanned 10 breeding seasons over 15 yr (1994-2008). Read More

Emerg Infect Dis 2019 06;25(6):1093-1100

Everglades virus (EVEV), subtype II within the Venezuelan equine encephalitis (VEE) virus complex, is a mosquitoborne zoonotic pathogen endemic to south Florida, USA. EVEV infection in humans is considered rare, probably because of the sylvatic nature of the vector, the Culex (Melanoconion) cedecei mosquito. The introduction of Cx. Read More

Sci Transl Med 2019 05;11(492)

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Western, Eastern, and Venezuelan equine encephalitis viruses (WEEV, EEEV, and VEEV, respectively) are important mosquito-borne agents that pose public health and bioterrorism threats. Despite considerable advances in understanding alphavirus replication, there are currently no available effective vaccines or antiviral treatments against these highly lethal pathogens. To develop a potential countermeasure for viral encephalitis, we generated a trivalent, or three-component, EEV vaccine composed of virus-like particles (VLPs). Read More

Vaccine 2019 05 6;37(25):3317-3325. Epub 2019 May 6.

Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA. Electronic address:

Novel live-attenuated V4020 vaccine was prepared for Venezuelan equine encephalitis virus (VEEV), an alphavirus from the Togaviridae family. The genome of V4020 virus was rearranged, with the capsid gene expressed using a duplicate subgenomic promoter downstream from the glycoprotein genes. V4020 also included both attenuating mutations from the TC83 VEEV vaccine secured by mutagenesis to prevent reversion mutations. Read More

Sci Rep 2019 05 6;9(1):6932. Epub 2019 May 6.

Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Self-replicating (replicon) RNA is a promising new platform for gene therapy, but applications are still limited by short persistence of expression in most cell types and low levels of transgene expression in vivo. To address these shortcomings, we developed an in vitro evolution strategy and identified six mutations in nonstructural proteins (nsPs) of Venezuelan equine encephalitis (VEE) replicon that promoted subgenome expression in cells. Two mutations in nsP2 and nsP3 enhanced transgene expression, while three mutations in nsP3 regulated this expression. Read More

J Virol Methods 2019 08 15;270:12-17. Epub 2019 Apr 15.

Diagnostic Systems Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, USA. Electronic address:

There is a pressing need for sustainable and sensitive immunodiagnostics for use in public health efforts to understand and combat the threat of endemic and emerging infectious diseases. In this proof-of-concept work, we describe an immunodiagnostic approach based on the utilization of virus-like particles (VLPs) in a magnetic bead-based platform for multiplexed detection of antiviral humoral response. A retroviral-based VLP, that presents Venezuelan equine encephalitis virus E1/E2 glycoprotein antigen on its surface, was synthesized and coupled to magnetic beads to create VLP-conjugated microspheres (VCMs). Read More

Antiviral Res 2019 07 7;167:25-34. Epub 2019 Apr 7.

Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin, Madison, WI, 53705-2222, USA. Electronic address:

Currently, there are no licensed human vaccines or antivirals for treatment of or prevention from infection with encephalitic alphaviruses. Because epidemics are sporadic and unpredictable, and endemic disease is common but rarely diagnosed, it is difficult to identify all populations requiring vaccination; thus, an effective post-exposure treatment method is needed to interrupt ongoing outbreaks. To address this public health need, we have continued development of ML336 to deliver a molecule with prophylactic and therapeutic potential that could be relevant for use in natural epidemics or deliberate release scenario for Venezuelan equine encephalitis virus (VEEV). Read More

Vector Borne Zoonotic Dis 2019 09 9;19(9):685-689. Epub 2019 Apr 9.

Department of Viral and Rickettsial Diseases, Naval Medical Research Center, Silver Spring, Maryland.

Dengue viruses (DENV) are currently responsible for more human morbidity and mortality than any other known arbovirus, and all four DENV are known to exist in sylvatic cycles that might allow these viruses to persist if the urban () cycle could be controlled. To determine whether DENV were being maintained in a sylvatic cycle in a forested area about 14 km southwest of Iquitos, Peru, a city in which all 4 serotypes of DENV circulate, we placed 20 DENV seronegative monkeys in cages either in the canopy or near ground level for a total of 125.6 months. Read More