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Viruses 2022 Jun 2;14(6). Epub 2022 Jun 2.

Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

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. Read More

Vet Sci 2022 May 28;9(6). Epub 2022 May 28.

Laboratory of Virology, Tropical Diseases Research Program (PIET), School of Veterinary Medicine, Universidad Nacional, Heredia 40101, Costa Rica.

Venezuelan Equine Encephalitis virus (VEEV) is an arboviral pathogen in tropical America that causes lethal encephalitis in horses and humans. VEEV is classified into six subtypes (I to VI). Subtype I viruses are divided into epizootic (IAB and IC) and endemic strains (ID and IE) that can produce outbreaks or sporadic diseases, respectively. Read More

PLoS Pathog 2022 Jun 13;18(6):e1009946. Epub 2022 Jun 13.

Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Venezuelan equine encephalitis virus (VEEV) is a positively-stranded RNA arbovirus of the genus Alphavirus that causes encephalitis in humans. Cynomolgus macaques are a relevant model of the human disease caused by VEEV and are useful in exploring pathogenic mechanisms and the host response to VEEV infection. Macaques were exposed to small-particle aerosols containing virus derived from an infectious clone of VEEV strain INH-9813, a subtype IC strain isolated from a human infection. Read More

Pharmaceuticals (Basel) 2022 May 17;15(5). Epub 2022 May 17.

National Center for Biotechnology, Korgalzhin hwy 13/5, Nur-Sultan 010000, Kazakhstan.

The synthetic compounds, Tilorone and Cridanimod, have the antiviral activity which initially had been ascribed to the capacity to induce interferon. Both drugs induce interferon in mice but not in humans. This study investigates whether these compounds have the antiviral activity in mice and rats since rats more closely resemble the human response. Read More

mBio 2022 May 25:e0073122. Epub 2022 May 25.

Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hanover, Germany.

Chikungunya virus (CHIKV) is an arthritogenic reemerging virus replicating in plasma membrane-derived compartments termed "spherules." Here, we identify the human transmembrane protein CD81 as host factor required for CHIKV replication. Ablation of CD81 results in decreased CHIKV permissiveness, while overexpression enhances infection. Read More

Lancet Infect Dis 2022 May 11. Epub 2022 May 11.

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

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. Read More

NPJ Vaccines 2022 Apr 22;7(1):46. Epub 2022 Apr 22.

U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, MD, 21702, USA.

We have previously shown that DNA vaccines expressing codon optimized alphavirus envelope glycoprotein genes protect both mice and nonhuman primates from viral challenge when delivered by particle-mediated epidermal delivery (PMED) or intramuscular (IM) electroporation (EP). Another technology with fewer logistical drawbacks is disposable syringe jet injection (DSJI) devices developed by PharmaJet, Inc. These needle-free jet injection systems are spring-powered and capable of delivering vaccines either IM or into the dermis (ID). Read More

ACS Med Chem Lett 2022 Apr 14;13(4):546-553. Epub 2022 Mar 14.

Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin 53705, United States.

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. Read More

PLoS Negl Trop Dis 2022 04 13;16(4):e0010329. Epub 2022 Apr 13.

University of Florida IFAS, Florida Medical Entomology Laboratory, Vero Beach, Florida, United States of America.

Determining effective sampling methods for mosquitoes are among the first objectives in elucidating transmission cycles of vector-borne zoonotic disease, as the effectiveness of sampling methods can differ based on species, location, and physiological state. The Spissipes section of the subgenus Melanoconion of Culex represents an understudied group of mosquitoes which transmit Venezuelan equine encephalitis viruses (VEEV) in the Western Hemisphere. The objective of this study was to determine effective collection methods that target both blood-engorged and non-engorged females of the Spissipes section of Culex subgenus Melanoconion to test the hypothesis that favorable trapping methods differ between species and by physiological status within a species. Read More

J Virol 2022 05 13;96(9):e0006422. Epub 2022 Apr 13.

Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA.

Alphaviruses infect cells by a low pH-dependent fusion reaction between viral and host cell membranes that is mediated by the viral E1 glycoprotein. Most reported alphavirus E1 sequences include two phenylalanines (F87 and F95) in the fusion loop, yet the role of these residues in viral infectivity remains to be defined. Following introduction of wild type (WT), E1-F87A, and E1-F95A chikungunya virus (CHIKV) RNA genomes into cells, viral particle production was similar in magnitude. Read More

Virus Evol 2021 Sep 17;7(2):veab105. Epub 2021 Dec 17.

Laboratório de Virologia Molecular, Instituto Carlos Chagas/Fiocruz-PR, Rua Prof. Algacyr Munhoz Mader 3775, Curitiba, PR 81350-010, Brazil.

Genomic and epidemiological surveillance are paramount for the discovery of new viruses with the potential to cross species barriers. Here, we present a new member of the genus found in and mosquitoes, tentatively named Pirahy virus (PIRAV). PIRAV was isolated from mosquito pools collected in a rural area of Piraí do Sul, South Brazil. Read More

J Exp Med 2022 04 17;219(4). Epub 2022 Mar 17.

Department of Medicine, Washington University School of Medicine, St. Louis, MO.

Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. Read More

Zoonoses (Burlingt) 2022 13;2. Epub 2022 Jan 13.

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, 77555, USA.

Background: Venezuelan equine encephalitis virus (VEEV) is an arbovirus endemic to the Americas. There are no approved vaccines or antivirals. TC-83 and V3526 are the best-characterized vaccine candidates for VEEV. Read More

Viruses 2022 01 28;14(2). Epub 2022 Jan 28.

Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM 87131, USA.

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. Read More

Cancer Gene Ther 2022 Feb 22. Epub 2022 Feb 22.

Replicate Bioscience, Inc., San Diego, CA, USA.

RNA technology has recently come to the forefront of innovative medicines and is being explored for a wide range of therapies, including prophylactic and therapeutic vaccines, biotherapeutic protein expression and gene therapy. In addition to conventional mRNA platforms now approved for prophylactic SARS-CoV2 vaccines, synthetic self-replicating RNA vaccines are currently being evaluated in the clinic for infectious disease and oncology. The prototypical srRNA vectors in clinical development are derived from alphaviruses, specifically Venezuelan Equine Encephalitis Virus (VEEV). Read More

Emerg Infect Dis 2022 Feb;28(2):445-448

We report a case of vertical transmission of Tonate virus in a pregnant woman from French Guiana. The fetus showed severe necrotic and hemorrhagic lesions of the brain and spinal cord. Clinicians should be made aware of possible adverse fetal outcomes in pregnant women infected with Tonate virus. Read More

EClinicalMedicine 2022 Feb 14;44:101262. Epub 2022 Jan 14.

Department of Infectious Disease, Imperial College London.

Background: Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19.

Methods: A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19 June to 28 October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0. Read More

Nucleic Acids Res 2022 01;50(2):1000-1016

Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore 636921.

Alphaviruses such as Ross River virus (RRV), chikungunya virus (CHIKV), Sindbis virus (SINV), and Venezuelan equine encephalitis virus (VEEV) are mosquito-borne pathogens that can cause arthritis or encephalitis diseases. Nonstructural protein 4 (nsP4) of alphaviruses possesses RNA-dependent RNA polymerase (RdRp) activity essential for viral RNA replication. No 3D structure has been available for nsP4 of any alphaviruses despite its importance for understanding alphaviral RNA replication and for the design of antiviral drugs. Read More

Emerg Microbes Infect 2022 Dec;11(1):465-476

Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China.

The extremely high transmission rate of SARS-CoV-2 and severe cases of COVID-19 pose the two critical challenges in the battle against COVID-19. Increasing evidence has shown that the viral spike (S) protein-driven syncytia may be responsible for these two events. Intensive attention has thus been devoted to seeking S-guided syncytium inhibitors. Read More

Sci Rep 2022 01 13;12(1):700. Epub 2022 Jan 13.

Center for Biomolecular Science and Engineering, U.S. Naval Research Laboratory, Washington, DC, USA.

Venezuelan equine encephalitis virus (VEEV) is a mosquito borne alphavirus which leads to high viremia in equines followed by lethal encephalitis and lateral spread to humans. In addition to naturally occurring outbreaks, VEEV is a potential biothreat agent with no approved human vaccine or therapeutic currently available. Single domain antibodies (sdAb), also known as nanobodies, have the potential to be effective therapeutic agents. Read More

Molecules 2021 Dec 3;26(23). Epub 2021 Dec 3.

Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Emerging viral infections, including those caused by dengue virus (DENV) and Venezuelan Equine Encephalitis virus (VEEV), pose a significant global health challenge. Here, we report the preparation and screening of a series of 4-anilinoquinoline libraries targeting DENV and VEEV. This effort generated a series of lead compounds, each occupying a distinct chemical space, including 3-((6-bromoquinolin-4-yl)amino)phenol (), 6-bromo--(5-fluoro-1H-indazol-6-yl)quinolin-4-amine () and 6-((6-bromoquinolin-4-yl)amino)isoindolin-1-one (), with EC values of 0. Read More

Viruses 2021 11 5;13(11). Epub 2021 Nov 5.

Defence Research and Development Canada, Suffield Research Centre, Medicine Hat, AB T1A 8K6, Canada.

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. Read More

BMC Infect Dis 2021 Oct 30;21(1):1121. Epub 2021 Oct 30.

Unidad de Desarrollo e Investigación en Bioprocesos (UDIBI), Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, México.

Background: More than 3 million infections were attributed to Chikungunya virus (CHIKV) in the 2014-2016 outbreak in Mexico, Central and South America, with over 500 deaths directly or indirectly related to this viral disease. CHIKV outbreaks are recurrent and no vaccine nor approved therapeutics exist to prevent or treat CHIKV infection. Reliable and robust diagnostic methods are thus critical to control future CHIKV outbreaks. Read More

NPJ Vaccines 2021 Oct 20;6(1):122. Epub 2021 Oct 20.

MSD Animal Health, Milton Keynes, UK.

Early in the SARS-CoV-2 pandemic concerns were raised regarding infection of new animal hosts and the effect on viral epidemiology. Infection of other animals could be detrimental by causing clinical disease, allowing further mutations, and bares the risk for the establishment of a non-human reservoir. Cats were the first reported animals susceptible to natural and experimental infection with SARS-CoV-2. Read More

Virus Res 2021 12 13;306:198598. Epub 2021 Oct 13.

National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, P. R. China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P. R. China; Beijing Engineering Research Center of Laboratory Medicine, Beijing Hospital, Beijing, P. R. China. Electronic address:

Background: Eastern equine encephalitis virus (EEEV), Western equine encephalitis virus (WEEV), Venezuelan equine encephalitis virus (VEEV), Hendra virus (HeV), Nipah virus (NiV), Yellow fever virus (YFV), West Nile virus (WNV), Saint Louis encephalitis virus (SLEV) and Tick-borne encephalitis virus (TBEV) have been detected in travelers returning to China and potentially pose a serious threat to public health. Real-time reverse transcription polymerase chain reaction (rRT-PCR) plays an important role in the detection of these viruses. Although these viruses are not mainly prevalent in China, occasionally imported cases have been reported with the increase in population mobility and entry-exit activities. Read More

Nature 2021 10 13;598(7882):677-681. Epub 2021 Oct 13.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences (CAS), Beijing, P. R. China.

Venezuelan equine encephalitis virus (VEEV) is an enveloped RNA virus that causes encephalitis and potentially mortality in infected humans and equines. At present, no vaccines or drugs are available that prevent or cure diseases caused by VEEV. Low-density lipoprotein receptor class A domain-containing 3 (LDLRAD3) was recently identified as a receptor for the entry of VEEV into host cells. Read More

Nature 2021 10 13;598(7882):672-676. Epub 2021 Oct 13.

Department of Pathology & Immunology, Washington University School of Medicine, St Louis, MO, USA.

LDLRAD3 is a recently defined attachment and entry receptor for Venezuelan equine encephalitis virus (VEEV), a New World alphavirus that causes severe neurological disease in humans. Here we present near-atomic-resolution cryo-electron microscopy reconstructions of VEEV virus-like particles alone and in a complex with the ectodomains of LDLRAD3. Domain 1 of LDLRAD3 is a low-density lipoprotein receptor type-A module that binds to VEEV by wedging into a cleft created by two adjacent E2-E1 heterodimers in one trimeric spike, and engages domains A and B of E2 and the fusion loop in E1. Read More

Virology 2022 01 28;565:13-21. Epub 2021 Sep 28.

Center for Vector-borne Infectious Diseases, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.

Eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV) and Venezuelan equine encephalitis virus (VEEV) can cause fatal encephalitis in humans and equids. Some MAbs to the E1 glycoprotein are known to be cross-reactive, weakly neutralizing in vitro but can protect from disease in animal models. We investigated the mechanism of neutralization of VEEV infection by the broadly cross-reactive E1-specific MAb 1A4B-6. Read More

Bioorg Med Chem Lett 2021 11 5;52:128407. Epub 2021 Oct 5.

Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Structural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address:

There is an urgent need for novel strategies for the treatment of emerging arthropod-borne viral infections, including those caused by dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV). We prepared and screened focused libraries of 4-anilinoquinolines and 4-anilinoquinazolines for antiviral activity and identified three potent compounds. N-(2,5-dimethoxyphenyl)-6-(trifluoromethyl)quinolin-4-amine (10) inhibited DENV infection with an EC = 0. Read More

Mol Ther Nucleic Acids 2021 Sep 24;25:483-493. Epub 2021 Jun 24.

Imperial College London, Department of Medicine, London W2 1PG, UK.

Self-amplifying mRNA (saRNA) represents a promising platform for nucleic acid delivery of vaccine immunogens. Unlike plasmid DNA, saRNA does not require entry into the nucleus of target cells for expression, having the capacity to drive higher protein expression compared to mRNA as it replicates within the cytoplasm. In this study, we examined the potential of stabilized native-like HIV-1 Envelope glycoprotein (Env) trimers to elicit immune responses when delivered by saRNA polyplexes (PLXs), assembled with linear polyethylenimine. Read More