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Viruses 2019 Feb 18;11(2). Epub 2019 Feb 18.

Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.

Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV is highly infectious in aerosol form and a known bio-warfare agent that can cause severe encephalitis in humans. Periodic outbreaks of VEEV occur predominantly in Central and South America. Read More

Mol Ther 2019 Jan 7. Epub 2019 Jan 7.

GSK, Rockville, MD 20850, USA. Electronic address:

Venezuelan equine encephalitis virus (VEEV) is a known biological defense threat. A live-attenuated investigational vaccine, TC-83, is available, but it has a high non-response rate and can also cause severe reactogenicity. We generated two novel VEE vaccine candidates using self-amplifying mRNA (SAM). Read More

Antiviral Res 2019 Feb 8. Epub 2019 Feb 8.

Center for Bio/molecular Science and Engineering, U.S. Naval Research Laboratory, Washington, DC 20375, USA. Electronic address:

The alphaviral nonstructural protein 2 (nsP2) cysteine proteases (EC 3.4.22. Read More

Antiviral Res 2019 Feb 8;164:61-69. Epub 2019 Feb 8.

National Center for Biodefense and Infectious Disease, School of Systems Biology, George Mason University, Manassas, VA, USA.

Venezuelan equine encephalitis virus (VEEV), a new world alphavirus belonging to the Togaviridae family, causes periodic disease outbreaks in humans and equines with high associated mortality and morbidity. VEEV is highly infectious via the aerosol route and so has been developed as a biological weapon (Hawley and Eitzen, 2001). Despite its current classification as a category B select agent, there are no FDA approved vaccines or therapeutics to counter VEEV infections. Read More

Klin Lab Diagn 2018 ;63(6):372-375

Federal State Budgetary Establishment «48 Central Scientific Research Institute» of the Ministry of the Defens of the Russian Federation, 141306, Sergiev Posad, Russian Federation.

The reverse transcription - polymerase chain reaction method (RT-PCR) has leading position on diagnostic infections, caused by RNA-containing viruses. This method presents severe requirements to carrying out of everybody stages of analysis (extraction of nucleic acid, carry out reverse transcription, amplification of DNA). It is necessary to account the possibility of false positive or false negative results appearance. Read More

Antiviral Res 2019 Mar 26;163:125-139. Epub 2019 Jan 26.

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

The New World alphaviruses, Venezuelan, eastern and western equine encephalitis viruses (VEEV, EEEV, and WEEV), are important human pathogens due to their ability to cause varying levels of morbidity and mortality in humans. There is also concern about VEEV and EEEV being used as bioweapons. Currently, a FDA-approved antiviral is lacking for New World alphaviruses. Read More

Curr Clin Microbiol Rep 2018 Dec 3;5(4):229-237. Epub 2018 Aug 3.

Department of Microbial Infection and Immunity, Infectious, Diseases Institute, The Ohio State University, 460 W 12th Ave, Biomedical Research Tower 790, Columbus, OH 43210, USA.

Purpose Of Review: Interferon-induced transmembrane protein 3 (IFITM3) is a cellular restriction factor that blocks fusion between virus and host membranes. Here, we provide an introduction to IFITM3 and the biochemical regulation underlying its antiviral activity. Further, we analyze and summarize the published literature examining phenotypes of IFITM3 knockout mice upon infections with viral pathogens and discuss the controversial association between single nucleotide polymorphisms (SNPs) in the human gene and severe virus infections. Read More

Antiviral Res 2019 Mar 11;163:59-69. Epub 2019 Jan 11.

Aix Marseille Université, CNRS, AFMB UMR 7257, Marseille, France; Unité des Virus Emergents (UVE: Aix-Marseille Univ-IRD 190-Inserm 1207-IHU Méditerranée Infection), Marseille, France. Electronic address:

Alphaviruses such as the Venezuelan equine encephalitis virus (VEEV) are important human emerging pathogens transmitted by mosquitoes. They possess a unique viral mRNA capping mechanism catalyzed by the viral non-structural protein nsP1, which is essential for virus replication. The alphaviruses capping starts by the methylation of a GTP molecule by the N7-guanine methyltransferase (MTase) activity; nsP1 then forms a covalent link with mGMP releasing pyrophosphate (GT reaction) and the mGMP is next transferred onto the 5'-diphosphate end of the viral mRNA to form a cap-0 structure. Read More

Front Microbiol 2018 18;9:3126. Epub 2018 Dec 18.

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

Venezuelan equine encephalitis virus (VEEV) is a positive sense, single-stranded RNA virus and member of the New World alphaviruses. It causes a biphasic febrile illness that can be accompanied by central nervous system involvement and moderate morbidity in humans and severe mortality in equines. The virus has a history of weaponization, lacks FDA-approved therapeutics and vaccines in humans, and is considered a select agent. Read More

Acta Trop 2019 Mar 19;191:178-184. Epub 2018 Dec 19.

Universidad de Córdoba, Instituto de Investigaciones Biológicas del Trópico, Montería, Colombia. Electronic address:

Alphavirus infection associated encephalitis is an emerging infectious disease with a high impact on public health in Latin America.

Objective: To study the eco-epidemiology of alphaviruses in bats of departments of Córdoba and Sucre, Colombia.

Methodology: A prospective descriptive cross-sectional study with a non-probabilistic sampling, in 12 localities of Córdoba and Sucre was carried out. Read More

PLoS One 2018 17;13(12):e0208851. Epub 2018 Dec 17.

Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

In response to the aggressive global spread of the mosquito-borne chikungunya virus (CHIKV), an accurate and accessible diagnostic tool is of high importance. CHIKV, an arthritogenic alphavirus, comprises three genotypes: East/Central/South African (ECSA), West African (WA), and Asian. A previous rapid immunochromatographic (IC) test detecting CHIKV E1 protein showed promising performance for detection of the ECSA genotype. Read More

Int J Mol Sci 2018 Nov 6;19(11). Epub 2018 Nov 6.

Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.

Adipose-derived mesenchymal stem cells (ADSCs) have attracted attention due to their potential for use in the treatment of various diseases. However, the self-renewal capacity of ADSCs is restricted and their function diminishes during passage. We previously generated induced tissue-specific stem cells from mouse pancreatic cells using a single synthetic self-replicating Venezuelan Equine Encephalitis (VEE)-reprogramming factor (RF) RNA replicon (SR-RNA) expressing the reprogramming factors POU class 5 homeobox 1 (OCT4), Krueppel-like factor 4 (KLF4), Sex determining region Y-box 2 (SOX2), and Glis Family Zinc Finger 1 (GLIS1). Read More

Viruses 2018 11 2;10(11). Epub 2018 Nov 2.

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

Venezuelan equine encephalitis virus (VEEV) is an arbovirus that is associated with robust inflammation that contributes to neurodegenerative phenotypes. In addition to triggering central nervous system (CNS) inflammation, VEEV will also induce mitochondrial dysfunction, resulting in increased cellular apoptosis. In this study, we utilize the TC-83 strain of VEEV to determine the role of mitochondrial oxidative stress in mediating inflammation elicited by murine brain microglial cells. Read More

Open Virol J 2018 31;12:80-98. Epub 2018 Aug 31.

ICAR-National Research Centre on Equines, Hisar-125001, India.

Introduction: Zoonotic diseases are the infectious diseases that can be transmitted to human beings and vice versa from animals either directly or indirectly. These diseases can be caused by a range of organisms including bacteria, parasites, viruses and fungi. Viral diseases are highly infectious and capable of causing pandemics as evidenced by outbreaks of diseases like Ebola, Middle East Respiratory Syndrome, West Nile, SARS-Corona, Nipah, Hendra, Avian influenza and Swine influenza. Read More

Comp Med 2018 Oct 3;68(5):380-395. Epub 2018 Oct 3.

Joint Vaccine Acquisition Program, Medical Countermeasure Systems, Fort Detrick, Maryland.

Licensure of medical countermeasure vaccines to protect against aerosolized Venezuelan equine encephalitis virus (VEEV) requires the use of the Animal Rule to assess vaccine efficacy, because human studies are not feasible or ethical. We therefore performed a retrospective study of VEE cases that occurred in at-risk laboratory workers and support personnel during the United States Biowarfare Program (1943-1969) to better define percutaneous- and aerosol-acquired VEE in humans and to compare these results with those described for the NHP model (in which high-dose aerosol VEEV challenge led to more severe encephalitis than parenteral challenge). Record review and analysis of 17 aerosol- and 23 percutaneous-acquired human cases of VEE included incubation period, symptoms, physical examination findings, and markers of infection. Read More

Antiviral Res 2018 Nov 27;159:113-121. Epub 2018 Sep 27.

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

We have previously shown that DNA vaccines expressing codon-optimized alphavirus envelope glycoprotein genes protect both mice and non-human primates from viral challenge when delivered by intramuscular electroporation (IM-EP). To determine if we could achieve equivalent immunogenicity and protective efficacy in the absence of electroporation, we co-delivered our Venezuelan equine encephalitis virus (VEEV) DNA vaccine with DNA plasmids expressing genetic adjuvants designed to augment immune responses. We tested the T1-inducing cytokine IL-12 as well as the granulocyte growth factor GM-CSF, both of which have demonstrated significant adjuvant effect when included in clinical DNA vaccine formulations. Read More

mSphere 2018 09 19;3(5). Epub 2018 Sep 19.

Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

Type I interferon (IFN)-stimulated genes (ISGs) have critical roles in inhibiting virus replication and dissemination. Despite advances in understanding the molecular basis of ISG restriction, the antiviral mechanisms of many remain unclear. The 20-kDa ISG ISG20 is a nuclear 3'-5' exonuclease with preference for single-stranded RNA (ssRNA) and has been implicated in the IFN-mediated restriction of several RNA viruses. Read More

Sci Rep 2018 Sep 18;8(1):13990. Epub 2018 Sep 18.

Department of Biotechnology and Bioengineering, Sandia National Laboratories, Livermore, CA, USA.

Venezuelan equine encephalitis virus (VEEV) poses a major public health risk due to its amenability for use as a bioterrorism agent and its severe health consequences in humans. ML336 is a recently developed chemical inhibitor of VEEV, shown to effectively reduce VEEV infection in vitro and in vivo. However, its limited solubility and stability could hinder its clinical translation. Read More

Sci Rep 2018 Sep 4;8(1):13487. Epub 2018 Sep 4.

Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology School of Biomedical Sciences, Monash University, Melbourne, Australia.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper. Read More

Lancet Child Adolesc Health 2017 Oct 10;1(2):134-146. Epub 2017 Aug 10.

Institut Pasteur, Biology of Infection Unit, Paris, France; Inserm U1117, Paris, France; Paris-Descartes University, Sorbonne Paris Cité, Centre d'Infectiologie Necker-Pasteur, Necker-Enfants Malades University Hospital, Institut Imagine, Assistance Publique-Hôpitaux de Paris, Paris, France. Electronic address:

Arboviruses are an expanding public health threat, with pregnant women facing unique complications from arbovirus infections. These infections, such as dengue and Crimean-Congo haemorrhagic fever, can be more severe in pregnant women than in the general population. Vertical transmission is reported for many arboviruses and can severely affect pregnancy outcome. Read More

Mamm Genome 2018 08 27;29(7-8):408-424. Epub 2018 Aug 27.

Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

Alphaviruses, members of the positive-sense, single-stranded RNA virus family Togaviridae, represent a re-emerging public health concern worldwide as mosquito vectors expand into new geographic ranges. Members of the alphavirus genus tend to induce clinical disease characterized by rash, arthralgia, and arthritis (chikungunya virus, Ross River virus, and Semliki Forest virus) or encephalomyelitis (eastern equine encephalitis virus, western equine encephalitis virus, and Venezuelan equine encephalitis virus), though some patients who recover from the initial acute illness may develop long-term sequelae, regardless of the specific infecting virus. Studies examining the natural disease course in humans and experimental infection in cell culture and animal models reveal that host genetics play a major role in influencing susceptibility to infection and severity of clinical disease. Read More

Virulence 2018 ;9(1):1403-1421

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

Venezuelan equine encephalitis virus (VEEV) is a neurotropic arbovirus that is highly infectious as an aerosol and can result in an encephalitic phenotype in infected individuals. VEEV infections are known to be associated with robust inflammation that eventually contributes to neurodegenerative phenotypes. In this study, we utilize the TC-83 strain of VEEV, which is known to induce the expression of IL-6, IL-8, and other pro-inflammatory cytokines. Read More

Vaccine 2018 08 20;36(34):5194-5203. Epub 2018 Jul 20.

Defence Research and Development Canada, Suffield Research Centre, Box 4000, Station Main, Medicine Hat, AB T1A 8K6, Canada.

The three encephalitic alphaviruses, western, eastern, and Venezuelan equine encephalitis viruses (WEEV, EEEV, and VEEV) are potential biothreat agents due to high infectivity through aerosol exposure, ease of production in large amounts, and relative stability in the environment. Currently, there is no licensed vaccine for human use to these three encephalitic alphaviruses, and efforts to move vaccine candidates forward into clinical trials have not been successful. In this study, the modified vaccinia Ankara-Bavarian Nordic (MVA-BN®) vaccine platform was used to construct and produce three monovalent recombinant MVA-BN-based encephalitic alphavirus vaccines, MVA-BN-W, MVA-BN-E, and MVA-BN-V. Read More

Emerg Infect Dis 2018 08;24(8):1578-1580

While studying respiratory infections in Peru, we identified Venezuelan equine encephalitis virus (VEEV) in a nasopharyngeal swab, indicating that this alphavirus can be present in human respiratory secretions. Because VEEV may be infectious when aerosolized, our finding is relevant for the management of VEEV-infected patients and for VEEV transmission studies. Read More

Antiviral Res 2018 Sep 5;157:57-67. Epub 2018 Jul 5.

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

The New World alphaviruses -Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV respectively) - cause a febrile disease that is often lethal in equines and children and leads to long-term neurological sequelae in survivors. Endemic to the Americas, epizootic outbreaks of the three viruses occur sporadically in the continental United States. All three viruses aerosolize readily, replicate to high titers in cell culture, and have low infectious doses. Read More

J Immunol Res 2018 3;2018:8521060. Epub 2018 Jun 3.

United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011, USA.

There remains a need for vaccines that can safely and effectively protect against the biological threat agents Venezuelan (VEEV), western (WEEV), and eastern (EEEV) equine encephalitis virus. Previously, we demonstrated that a VEEV DNA vaccine that was optimized for increased antigen expression and delivered by intramuscular (IM) electroporation (EP) elicited robust and durable virus-specific antibody responses in multiple animal species and provided complete protection against VEEV aerosol challenge in mice and nonhuman primates. Here, we performed a comparative evaluation of the immunogenicity and protective efficacy of individual optimized VEEV, WEEV, and EEEV DNA vaccines with that of a 1 : 1 : 1 mixture of these vaccines, which we have termed the 3-EEV DNA vaccine, when delivered by IM EP. Read More

Trends Microbiol 2018 Oct 11;26(10):877-885. Epub 2018 Jun 11.

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

Zika virus (ZIKV) has challenged the assumed knowledge regarding the pathobiology of flaviviruses. Despite causing sporadic and mild disease in the 50 years since its discovery, Zika virus has now caused multiple outbreaks in dozens of countries worldwide. Moreover, the disease severity in recent outbreaks, with neurological disease in adult and devastating congenital malformations in fetuses, was not previously seen. Read More

J Pharm Sci 2018 Oct 5;107(10):2544-2558. Epub 2018 Jun 5.

Macromolecule and Vaccine Stabilization Center, Department of Pharmaceutical Chemistry, University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047. Electronic address:

The zoonotic equine encephalitis viruses (EEVs) can cause debilitating and life-threatening disease, leading to ongoing vaccine development efforts for an effective virus-like particle (VLP) vaccine based on 3 strains of EEV (Eastern, Western, and Venezuelan or EEE, WEE and VEE VLPs, respectively). In this work, transmission electron microscopy and light scattering studies showed enveloped, spherical, and ∼70 nm sized VLPs. Biophysical studies demonstrated optimal VLP physical stability in the pH range of 7. Read More

Med Chem 2018 May 23. Epub 2018 May 23.

Pharmaceutical Sciences Department, College of Pharmacy, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064. United States.

Background: Search for new antiviral and anticancer agents are essential because of the emergence of drug resistance in recent years. In continuation of our efforts in identifying the new small molecule antiviral and anticancer agents, we identified chalcones as potent antiviral and anticancer agents.

Objective: With the aim of identifying the broad acting antiviral and anticancer agents, we discovered substituted aryl/heteroaryl derived thienyl chalcones as antiviral and anticancer agents. Read More

J Virol 2018 08 17;92(15). Epub 2018 Jul 17.

National Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, Virginia, USA

Protein phosphatase 1 (PP1) is a serine/threonine phosphatase which has been implicated in the regulation of a number of viruses, including HIV-1, Ebolavirus, and Rift Valley fever virus. Catalytic subunits of PP1 (PP1α, PP1β, and PP1γ) interact with a host of regulatory subunits and target a wide variety of cellular substrates through a combination of short binding motifs, including an RVxF motif present in the majority of PP1 regulatory subunits. Targeting the RVxF-interacting site on PP1 with the small molecule 1E7-03 inhibits HIV-1, Ebolavirus, and Rift Valley fever virus replication. Read More

Am J Trop Med Hyg 2018 Jun 3;98(6):1798-1804. Epub 2018 May 3.

Departments of Microbiology & Immunology and Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, Texas.

Members of the genera (family ) and (family ) are important zoonotic human and equine etiologic agents of neurologic diseases in the New World. In 2010, an outbreak of Madariaga virus (MADV; formerly eastern equine encephalitis virus) and Venezuelan equine encephalitis virus (VEEV) infections was reported in eastern Panamá. We further characterized the epidemiology of the outbreak by studying household contacts of confirmed human cases and of equine cases with neurological disease signs. Read More

Clin Infect Dis 2018 Aug;67(4):619-621

Department of Infectious Diseases and Tropical Medicine, Instituto Diagnóstico Barquisimeto (IDB)/ Biomedical Research Institute/IDB Hospital, Barquisimeto, Lara.

We report identification of Madariaga virus (MADV) in plasma and urine samples from a child with acute undifferentiated febrile illness in Venezuela. Our data document the occurrence of milder MADV infections (ie, without encephalitis), with a symptom complex that resembles that seen with other arboviral infections, including dengue and zika. Read More

Emerg Infect Dis 2018 05;24(5):821-826

The introduction and spread of West Nile virus and the recent introduction of chikungunya and Zika viruses into the Americas have raised concern about the potential for various tropical pathogens to become established in North America. A historical analysis of yellow fever and malaria incidences in the United States suggests that it is not merely a temperate climate that keeps these pathogens from becoming established. Instead, socioeconomic changes are the most likely explanation for why these pathogens essentially disappeared from the United States yet remain a problem in tropical areas. Read More

Vector Borne Zoonotic Dis 2018 05 13;18(5):266-272. Epub 2018 Mar 13.

1 Research Institute in Health Sciences, National University of Asunción , San Lorenzo, Paraguay .

Introduction: Alphaviruses can produce febrile illness and encephalitis in dead-end hosts such as horses and humans. Within this genus, the Venezuelan Equine Encephalitis virus (VEEV) complex includes pathogenic epizootic subtypes and enzootic subtypes that are not pathogenic in horses (except subtype IE, Mexican strains), although they can cause febrile symptoms in humans. The Rio Negro virus (RNV-VEEV subtype VI) circulates in Argentina, where it was associated with undifferentiated febrile illness. Read More

Am J Trop Med Hyg 2018 Jun 5;98(6):1811-1818. Epub 2018 Apr 5.

Sección Virología, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.

Alphaviruses () are arboviruses frequently associated with emerging infectious diseases. In this study, we aimed to investigate the presence of alphaviruses in Uruguay by detecting the viral genome in mosquitoes and neutralizing antibodies in equines. A total of 3,575 mosquitoes were analyzed for alphavirus genome detection. Read More

Sci Rep 2018 Apr 3;8(1):5417. Epub 2018 Apr 3.

MRIGlobal, 65 West Watkins Mill Road, Gaithersburg, MD, 20878, USA.

The future of infectious disease surveillance and outbreak response is trending towards smaller hand-held solutions for point-of-need pathogen detection. Here, samples of Culex cedecei mosquitoes collected in Southern Florida, USA were tested for Venezuelan Equine Encephalitis Virus (VEEV), a previously-weaponized arthropod-borne RNA-virus capable of causing acute and fatal encephalitis in animal and human hosts. A single 20-mosquito pool tested positive for VEEV by quantitative reverse transcription polymerase chain reaction (RT-qPCR) on the Biomeme two3. Read More

Virus Evol 2018 Jan 6;4(1):vey004. Epub 2018 Mar 6.

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

During RNA virus replication, there is the potential to incorporate mutations that affect virulence or pathogenesis. For live-attenuated vaccines, this has implications for stability, as replication may result in mutations that either restore the wild-type phenotype via reversion or compensate for the attenuating mutations by increasing virulence (pseudoreversion). Recent studies have demonstrated that altering the mutation rate of an RNA virus is an effective attenuation tool. Read More

mSphere 2018 Mar-Apr;3(2). Epub 2018 Mar 21.

Molecular and Translational Sciences Division, Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, USA.

Mayaro virus (MAYV), Venezuelan equine encephalitis virus (VEEV), and chikungunya virus (CHIKV) are vector-borne alphaviruses that cocirculate in South America. Human infections by these viruses are frequently underdiagnosed or misdiagnosed, especially in areas with high dengue virus endemicity. Disease may progress to debilitating arthralgia (MAYV, CHIKV), encephalitis (VEEV), and death. Read More

Zoonoses Public Health 2018 08 25;65(5):505-511. Epub 2018 Mar 25.

Pathobiology, School of Veterinary Medicine, St. George's University, St. George, Grenada.

Antibody detection against selected potentially zoonotic vector-borne alphaviruses and flaviviruses was conducted on sera from bats from all six parishes in Grenada, West Indies. Sera were tested for (i) antibodies to flaviviruses West Nile virus, St. Louis encephalitis virus, Ilhéus virus, Bussuquara virus (BSQV), Rio Bravo virus and all four serotypes of dengue virus (DENV) by plaque reduction neutralization test (PRNT); (ii) antibodies to alphaviruses western equine encephalitis virus, Venezuelan equine encephalitis virus and eastern equine encephalitis virus by epitope-blocking enzyme-linked immunosorbent assay (ELISA); and (iii) antibodies to the alphavirus chikungunya (CHIKV) by PRNT. Read More

J Virol 2018 06 14;92(11). Epub 2018 May 14.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Read More

Equine Vet J 2018 Jul 14;50(4):436-445. Epub 2018 Apr 14.

School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington, Leicestershire, UK.

Equine populations worldwide are at increasing risk of infection by viruses transmitted by biting arthropods, including mosquitoes, biting midges (Culicoides), sandflies and ticks. These include the flaviviruses (Japanese encephalitis, West Nile and Murray Valley encephalitis), alphaviruses (eastern, western and Venezuelan encephalitis) and the orbiviruses (African horse sickness and equine encephalosis). This review provides an overview of the challenges faced in the surveillance, prevention and control of the major equine arboviruses, particularly in the context of these viruses emerging in new regions of the world. Read More

Virus Evol 2018 Jan 15;4(1):vey001. Epub 2018 Feb 15.

Department of Pathology, Institute for Human Infections and Immunity, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0610, USA.

Viral diversity is theorized to play a significant role during virus infections, particularly for arthropod-borne viruses (arboviruses) that must infect both vertebrate and invertebrate hosts. To determine how viral diversity influences mosquito infection and dissemination mosquitoes were infected with the Venezuelan equine encephalitis virus endemic strain 68U201. Bodies and legs/wings of the mosquitoes were collected individually and subjected to multi-parallel sequencing. Read More

Insect Sci 2018 Feb 14. Epub 2018 Feb 14.

Department of Molecular and Cellular Biology, University of California-Davis, Davis, California, USA.

Culex mosquitoes are primarily found in temperate and tropical regions worldwide where they play a crucial role as main vectors of filarial worms and arboviruses. In Recife, a northeast city in Brazil, high densities of Culex quinquefasciatus are often found in association with human populated areas. In marked contrast to another part of the city, field tests conducted in the neighborhood of Sítio dos Pintos showed that trapping of mosquitoes in skatole-baited ovitraps did not differ significantly from captures in control (water) traps. Read More

J Virol Methods 2018 04;254:31-34

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

Working with virological samples requires validated inactivation protocols for safe handling and disposal. Although many techniques exist to inactivate samples containing viruses, not all procedures have been properly validated or are compatible with subsequent assays. To aid in the development of inactivation protocols for Alphaviruses, and specifically Venezuelan equine encephalitis virus (VEEV), a variety of methods were evaluated for their ability to completely inactivate a high titer sample of the vaccine strain VEEV TC-83. Read More

Nucleic Acids Res 2018 Apr;46(7):3657-3670

Department of Biology, UNC-Chapel Hill, USA.

Alphaviruses are mosquito-borne pathogens that cause human diseases ranging from debilitating arthritis to lethal encephalitis. Studies with Sindbis virus (SINV), which causes fever, rash, and arthralgia in humans, and Venezuelan equine encephalitis virus (VEEV), which causes encephalitis, have identified RNA structural elements that play key roles in replication and pathogenesis. However, a complete genomic structural profile has not been established for these viruses. Read More

Antiviral Res 2018 03 11;151:8-19. Epub 2018 Jan 11.

Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Melbourne, Australia. Electronic address:

Although the alphavirus Venezuelan equine encephalitis virus (VEEV) has been the cause of multiple outbreaks resulting in extensive human and equine mortality and morbidity, there are currently no anti-VEEV therapeutics available. VEEV pathogenicity is largely dependent on targeting of the viral capsid protein (CP) to the host cell nucleus through the nuclear transporting importin (Imp) α/β1 heterodimer. Here we perform a high-throughput screen, combined with nested counterscreens to identify small molecules able to inhibit the Impα/β1:CP interaction for the first time. Read More

Virology 2018 02 5;515:223-234. Epub 2018 Jan 5.

Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India. Electronic address:

The crystal structure of chikungunya (CHIKV) virus capsid protease domain has been determined at 2.2Å. Structure reveals a chymotrypsin-like protease fold with a conserved hydrophobic pocket in CHIKV capsid protein (CP) for interaction with the cytoplasmic tail of E2 (cdE2) similar to the capsid protein of other alphaviruses. Read More

Vaccine 2018 01 26;36(5):683-690. Epub 2017 Dec 26.

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:

Lassa virus (LASV) is the most prevalent rodent-borne arenavirus circulated in West Africa. With population at risk from Senegal to Nigeria, LASV causes Lassa fever and is responsible for thousands of deaths annually. High genetic diversity of LASV is one of the challenges for vaccine R&D. Read More

J Virol 2018 03 26;92(6). Epub 2018 Feb 26.

Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, Oregon, USA

The type I interferon (IFN) system represents an essential innate immune response that renders cells resistant to virus growth via the molecular actions of IFN-induced effector proteins. IFN-mediated cellular states inhibit growth of numerous and diverse virus types, including those of known pathogenicity as well as potentially emerging agents. As such, targeted pharmacologic activation of the IFN response may represent a novel therapeutic strategy to prevent infection or spread of clinically impactful viruses. Read More

Sci Rep 2017 Dec 18;7(1):17705. Epub 2017 Dec 18.

Nuclear Signaling Laboratory, Department of Biochemistry and Molecular Biology School of Biomedical Sciences, Monash University, Melbourne, Australia.

Therapeutics are currently unavailable for Venezuelan equine encephalitis virus (VEEV), which elicits flu-like symptoms and encephalitis in humans, with an estimated 14% of cases resulting in neurological disease. Here we identify anti-VEEV agents using in silico structure-based-drug-design (SBDD) for the first time, characterising inhibitors that block recognition of VEEV capsid protein (C) by the host importin (IMP) α/β1 nuclear transport proteins. From an initial screen of 1. Read More