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    Characterization of monkeypox virus infection in African rope squirrels (Funisciurus sp.).
    PLoS Negl Trop Dis 2017 Aug 21;11(8):e0005809. Epub 2017 Aug 21.
    US Geological Survey, National Wildlife Health Center, Madison, Wisconsin, United States of America.
    Monkeypox (MPX) is a zoonotic disease endemic in Central and West Africa and is caused by Monkeypox virus (MPXV), the most virulent orthopoxvirus affecting humans since the eradication of Variola virus (VARV). Many aspects of the MPXV transmission cycle, including the natural host of the virus, remain unknown. African rope squirrels (Funisciurus spp. Read More

    FDG Uptake in Lymphoid Tissue serves as a Predictor of Disease Outcome in the Nonhuman Primate Model of Monkeypox Infection.
    J Virol 2017 Aug 16. Epub 2017 Aug 16.
    Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Frederick, Maryland, United States of America.
    Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections using in vivo imaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [(18)F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progression in vivo in nonhuman primates (NHPs). Read More

    Evaluation of Taterapox Virus in Small Animals.
    Viruses 2017 Aug 1;9(8). Epub 2017 Aug 1.
    Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1100 South Grand Boulevard, St. Louis, MO 63104, USA.
    Taterapox virus (TATV), which was isolated from an African gerbil (Tatera kempi) in 1975, is the most closely related virus to variola; however, only the original report has examined its virology. We have evaluated the tropism of TATV in vivo in small animals. We found that TATV does not infect Graphiurus kelleni, a species of African dormouse, but does induce seroconversion in the Mongolian gerbil (Meriones unguiculatus) and in mice; however, in wild-type mice and gerbils, the virus produces an unapparent infection. Read More

    Insufficient Innate Immunity Contributes to the Susceptibility of the Castaneous Mouse to Orthopoxvirus Infection.
    J Virol 2017 Jul 26. Epub 2017 Jul 26.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892
    The castaneous (CAST) mouse, a wild-derived inbred strain, is highly susceptible to orthopoxvirus infection by intranasal and systemic routes. The 50% lethal intraperitoneal dose of vaccinia virus (VACV) was 3 PFU for CAST mice, whereas BALB/c mice survived 10(6) PFU. At all times and in all organs analyzed, virus titers were higher in CAST than in BALB/c mice. Read More

    Vaccinia virus and Cowpox virus are not susceptible to the interferon-induced antiviral protein MxA.
    PLoS One 2017 20;12(7):e0181459. Epub 2017 Jul 20.
    Departamento de Biotecnología, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (I.N.I.A.), Madrid, Spain.
    MxA protein is expressed in response to type I and type III Interferon and constitute an important antiviral factor with broad antiviral activity to diverse RNA viruses. In addition, some studies expand the range of MxA antiviral activity to include particular DNA viruses like Monkeypox virus (MPXV) and African Swine Fever virus (ASFV). However, a broad profile of activity of MxA to large DNA viruses has not been established to date. Read More

    Comparative Efficacy of Intramuscular and Scarification Routes of Administration of Live Smallpox Vaccine in a Murine Challenge Model.
    Vaccine 2017 Jul 9;35(31):3889-3896. Epub 2017 Jun 9.
    CBR Division, Dstl Porton Down, Salisbury SP4 0JQ, UK; The Pirbright Institute, Ash Road, Woking GU24 0NF, UK. Electronic address:
    In recent years concern has mounted regarding the possibility of a re-emergence of smallpox through biowarfare or bioterrorism. There is also concern over the incidence of human monkeypox in endemic areas and the potential for monkeypox to be accidentally transported to non-endemic areas. In the event of re-emergence of smallpox or emergence of monkeypox, the accepted route of administration for live replicating smallpox vaccine is dermal scarification, which generates a virus-shedding lesion that persists for several days at the vaccination site. Read More

    Review of poxvirus: emergence of monkeypox.
    Med Sante Trop 2017 Feb;27(1):29-39
    Service de dermatologie, HIA Sainte-Anne, Toulon, France.
    This article reviews the different types of poxvirus infections. Smallpox, although eradicated, must continue to be monitored because of the potential risk of accidental or voluntary (by bioterrorism) reintroduction. Monkeypox and cowpox viruses are considered to be emergent today ; their high risk of dissemination is due to the increase in international transport as well as trends for new animals as pets and the loss of vaccinal protection against smallpox. Read More

    Monkeypox Virus Host Factor Screen Using Haploid Cells Identifies Essential Role of GARP Complex in Extracellular Virus Formation.
    J Virol 2017 Jun 12;91(11). Epub 2017 May 12.
    Poxvirus and Rabies Branch, Division of High Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
    Monkeypox virus (MPXV) is a human pathogen that is a member of the Orthopoxvirus genus, which includes Vaccinia virus and Variola virus (the causative agent of smallpox). Human monkeypox is considered an emerging zoonotic infectious disease. To identify host factors required for MPXV infection, we performed a genome-wide insertional mutagenesis screen in human haploid cells. Read More

    Presumptive risk factors for monkeypox in rural communities in the Democratic Republic of the Congo.
    PLoS One 2017 13;12(2):e0168664. Epub 2017 Feb 13.
    US Centers for Disease Control and Prevention, Poxvirus and Rabies Branch, Atlanta, Georgia, United States of America.
    Monkeypox virus (MPXV), a close relative of Variola virus, is a zoonotic virus with an unknown reservoir. Interaction with infected wildlife, bites from peri-domestic animals, and bushmeat hunting are hypothesized routes of infection from wildlife to humans. Using a Risk Questionnaire, performed in monkeypox-affected areas of rural Democratic Republic of the Congo, we describe the lifestyles and demographics associated with presumptive risk factors for MPXV infection. Read More

    A rapid Orthopoxvirus purification protocol suitable for high-containment laboratories.
    J Virol Methods 2017 May 26;243:68-73. Epub 2017 Jan 26.
    Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
    Virus purification in a high-containment setting provides unique challenges due to barrier precautions and operational safety approaches that are not necessary in lower biosafety level (BSL) 2 environments. The need for high risk group pathogen diagnostic assay development, anti-viral research, pathogenesis and vaccine efficacy research necessitates work in BSL-3 and BSL-4 labs with infectious agents. When this work is performed in accordance with BSL-4 practices, modifications are often required in standard protocols. Read More

    Buccal viral DNA as a trigger for brincidofovir therapy in the mousepox model of smallpox.
    Antiviral Res 2017 Mar 27;139:112-116. Epub 2016 Dec 27.
    Saint Louis University School of Medicine, 1100 S. Grand Blvd, St. Louis, MO 63104, USA. Electronic address:
    Orthopoxviruses continue to pose a significant threat to the population as potential agents of bioterrorism. An intentional release of natural or engineered variola virus (VARV) or monkeypox viruses would cause mortality and morbidity in the target population. To address this, antivirals have been developed and evaluated in animal models of smallpox and monkeypox. Read More

    A Single Vaccination of Nonhuman Primates with Highly Attenuated Smallpox Vaccine, LC16m8, Provides Long-term Protection against Monkeypox.
    Jpn J Infect Dis 2017 Jul 22;70(4):408-415. Epub 2016 Dec 22.
    Laboratory of Special Pathogens, Department of Virology 1, National Institute of Infectious Diseases.
    Monkeypox virus (MPXV) causes human monkeypox (human MPX), which is a similar disease to smallpox in humans. A previous study showed that a single vaccination of monkeys with LC16m8, a highly attenuated smallpox vaccine, protected them from MPX from 4-5 weeks post-vaccination. In this study, we evaluated the long-term efficacy of a single vaccination with LC16m8 in a nonhuman primate model of MPXV infection. Read More

    Evaluation of the GeneXpert for Human Monkeypox Diagnosis.
    Am J Trop Med Hyg 2017 Feb 19;96(2):405-410. Epub 2016 Dec 19.
    Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Enteric and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia.
    Monkeypox virus (MPXV), a zoonotic orthopoxvirus (OPX), is endemic in the Democratic Republic of Congo (DRC). Currently, diagnostic assays for human monkeypox (MPX) focus on real-time quantitative polymerase chain reaction (PCR) assays, which are typically performed in sophisticated laboratory settings. Herein, we evaluated the accuracy and utility of a multiplex MPX assay using the GeneXpert platform, a portable rapid diagnostic device that may serve as a point-of-care test to diagnose infections in endemic areas. Read More

    Rapid and sensitive point-of-care detection of Orthopoxviruses by ABICAP immunofiltration.
    Virol J 2016 Dec 9;13(1):207. Epub 2016 Dec 9.
    Centre for Biological Threats and Special Pathogens (ZBS), Robert Koch Institute, Seestrasse 10, 13353, Berlin, Germany.
    Background: The rapid and reliable detection of infectious agents is one of the most challenging tasks in scenarios lacking well-equipped laboratory infrastructure, like diagnostics in rural areas of developing countries. Commercially available point-of-care diagnostic tests for emerging and rare diseases are particularly scarce.

    Results: In this work we present a point-of-care test for the detection of Orthopoxviruses (OPV). Read More

    Integration of Global Analyses of Host Molecular Responses with Clinical Data To Evaluate Pathogenesis and Advance Therapies for Emerging and Re-emerging Viral Infections.
    ACS Infect Dis 2016 Nov 5;2(11):787-799. Epub 2016 Aug 5.
    Critical Care Medicine Department, Clinical Center, National Institutes of Health , Bethesda, Maryland 20814, United States.
    Outbreaks associated with emerging and re-emerging viral pathogens continue to increase in frequency and are associated with an increasing burden to global health. In light of this, there is a need to integrate basic and clinical research for investigating the connections between molecular and clinical pathogenesis and for therapeutic development strategies. Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis. Read More

    [Twelve cases of monkeypox virus outbreak in Bangassou District (Central African Republic) in December 2015].
    Bull Soc Pathol Exot 2016 Dec 25;109(5):358-363. Epub 2016 Oct 25.
    Unité des mycobactéries, Service de laboratoire, Hôpital de l'Amitié, Bangui, République centrafricaine.
    An outbreak of monkeypox occurred in the district of Bangassou in 2015. The monkeypox is a re-emerging zoonosis of viral origin highly contagious. It is an eruptive fever which evolves in an epidemic manner. Read More

    Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.
    Cell 2016 Oct;167(3):684-694.e9
    The Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. Electronic address:
    Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Read More

    Protection of mice against the highly pathogenic VVIHD-J by DNA and fowlpox recombinant vaccines, administered by electroporation and intranasal routes, correlates with serum neutralizing activity.
    Antiviral Res 2016 Oct 13;134:182-191. Epub 2016 Sep 13.
    Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, 20133 Milano, Italy; Cellular and Molecular Pharmacology Section, National Research Council (CNR), Institute of Neurosciences, University of Milan, Via Vanvitelli, 32, 20129 Milano, Italy. Electronic address:
    The control of smallpox was achieved using live vaccinia virus (VV) vaccine, which successfully eradicated the disease worldwide. As the variola virus no longer exists as a natural infection agent, mass vaccination was discontinued after 1980. However, emergence of smallpox outbreaks caused by accidental or deliberate release of variola virus has stimulated new research for second-generation vaccine development based on attenuated VV strains. Read More

    Finishing monkeypox genomes from short reads: assembly analysis and a neural network method.
    BMC Genomics 2016 Aug 31;17 Suppl 5:497. Epub 2016 Aug 31.
    Poxvirus and Rabies Branch, Division of High Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, 30333, USA.
    Background: Poxviruses constitute one of the largest and most complex animal virus families known. The notorious smallpox disease has been eradicated and the virus contained, but its simian sister, monkeypox is an emerging, untreatable infectious disease, killing 1 to 10 % of its human victims. In the case of poxviruses, the emergence of monkeypox outbreaks in humans and the need to monitor potential malicious release of smallpox virus requires development of methods for rapid virus identification. Read More

    Species-specific differentiation of variola, monkeypox, and varicella-zoster viruses by multiplex real-time PCR assay.
    J Virol Methods 2016 Oct 28;236:215-20. Epub 2016 Jul 28.
    State Research Center of Virology and Biotechnology "VECTOR", Koltsovo, Novosibirsk Region, 630559, Russia. Electronic address:
    A method of one-stage rapid detection and differentiation of epidemiologically important variola virus (VARV), monkeypox virus (MPXV), and varicella-zoster virus (VZV) utilizing multiplex real-time TaqMan PCR assay was developed. Four hybridization probes with various fluorescent dyes and the corresponding fluorescence quenchers were simultaneously used for the assay. The hybridization probes specific for the VARV sequence contained FAM/BHQ1 as a dye/quencher pair; MPXV-specific, JOE/BHQ1; VZV-specific, TAMRA/BHQ2; and internal control-specific, Cy5/BHQ3. Read More

    Monkeypox virus induces the synthesis of less dsRNA than vaccinia virus, and is more resistant to the anti-poxvirus drug, IBT, than vaccinia virus.
    Virology 2016 Oct 26;497:125-35. Epub 2016 Jul 26.
    School of Life Sciences, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA; The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, MC5401, Tempe, AZ 85287-5401, USA. Electronic address:
    Monkeypox virus (MPXV) infection fails to activate the host anti-viral protein, PKR, despite lacking a full-length homologue of the vaccinia virus (VACV) PKR inhibitor, E3. Since PKR can be activated by dsRNA produced during a viral infection, we have analyzed the accumulation of dsRNA in MPXV-infected cells. MPXV infection led to less accumulation of dsRNA than VACV infection. Read More

    Retrograde Transport from Early Endosomes to the trans-Golgi Network Enables Membrane Wrapping and Egress of Vaccinia Virus Virions.
    J Virol 2016 Oct 12;90(19):8891-905. Epub 2016 Sep 12.
    Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
    Unlabelled: The anterograde pathway, from the endoplasmic reticulum through the trans-Golgi network to the cell surface, is utilized by trans-membrane and secretory proteins. The retrograde pathway, which directs traffic in the opposite direction, is used following endocytosis of exogenous molecules and recycling of membrane proteins. Microbes exploit both routes: viruses typically use the anterograde pathway for envelope formation prior to exiting the cell, whereas ricin and Shiga-like toxins and some nonenveloped viruses use the retrograde pathway for cell entry. Read More

    Extended Human-to-Human Transmission during a Monkeypox Outbreak in the Democratic Republic of the Congo.
    Emerg Infect Dis 2016 Jun;22(6):1014-21
    A 600-fold increase in monkeypox cases occurred in the Bokungu Health Zone of the Democratic Republic of the Congo during the second half of 2013; this increase prompted an outbreak investigation. A total of 104 possible cases were reported from this health zone; among 60 suspected cases that were tested, 50 (48.1%) cases were confirmed by laboratory testing, and 10 (9. Read More

    Use of Vaccinia Virus Smallpox Vaccine in Laboratory and Health Care Personnel at Risk for Occupational Exposure to Orthopoxviruses - Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2015.
    MMWR Morb Mortal Wkly Rep 2016 Mar 18;65(10):257-62. Epub 2016 Mar 18.
    On June 25, 2015, the Advisory Committee on Immunization Practices (ACIP) recommended routine vaccination with live smallpox (vaccinia) vaccine (ACAM2000) for laboratory personnel who directly handle 1) cultures or 2) animals contaminated or infected with replication-competent vaccinia virus, recombinant vaccinia viruses derived from replication-competent vaccinia strains (i.e., those that are capable of causing clinical infection and producing infectious virus in humans), or other orthopoxviruses that infect humans (e. Read More

    Development of a Genus-Specific Antigen Capture ELISA for Orthopoxviruses - Target Selection and Optimized Screening.
    PLoS One 2016 1;11(3):e0150110. Epub 2016 Mar 1.
    Highly Pathogenic Viruses (ZBS 1), Centre for Biological Threats and Special Pathogens, Robert Koch Institute, Berlin, Germany.
    Orthopoxvirus species like cowpox, vaccinia and monkeypox virus cause zoonotic infections in humans worldwide. Infections often occur in rural areas lacking proper diagnostic infrastructure as exemplified by monkeypox, which is endemic in Western and Central Africa. While PCR detection requires demanding equipment and is restricted to genome detection, the evidence of virus particles can complement or replace PCR. Read More

    New effective chemically synthesized anti-smallpox compound NIOCH-14.
    J Gen Virol 2016 May 8;97(5):1229-39. Epub 2016 Feb 8.
    1​State Research Center of Virology and Biotechnology Vector (SRC VB Vector),Koltsovo, Novosibirsk region,Russian Federation.
    Antiviral activity of the new chemically synthesized compound NIOCH-14 (a derivative of tricyclodicarboxylic acid) in comparison with ST-246 (the condensed derivative of pyrroledione) was observed in experiments in vitro and in vivo using orthopoxviruses including highly pathogenic ones. After oral administration of NIOCH-14 to outbred ICR mice infected intranasally with 100 % lethal dose of ectromelia virus, it was shown that 50 % effective doses of NIOCH-14 and ST-246 did not significantly differ. The 'therapeutic window' varied from 1 day before infection to 6 days post-infection (p. Read More

    Evidence for Persistence of Ectromelia Virus in Inbred Mice, Recrudescence Following Immunosuppression and Transmission to Naïve Mice.
    PLoS Pathog 2015 Dec 23;11(12):e1005342. Epub 2015 Dec 23.
    Department of Immunology and Infectious Disease, John Curtin School of Medical Research, Australian National University, Canberra, Australia.
    Orthopoxviruses (OPV), including variola, vaccinia, monkeypox, cowpox and ectromelia viruses cause acute infections in their hosts. With the exception of variola virus (VARV), the etiological agent of smallpox, other OPV have been reported to persist in a variety of animal species following natural or experimental infection. Despite the implications and significance for the ecology and epidemiology of diseases these viruses cause, those reports have never been thoroughly investigated. Read More

    Pox-like lesions and haemorrhagic fever in two concurrent cases in the Central African Republic: case investigation and management in difficult circumstances.
    Pan Afr Med J 2015 10;22:23. Epub 2015 Sep 10.
    Hôpital Préfectoral de Batangafo, Central African Republic.
    Cases of monkeypox in humans are frequently reported from the Democratic Republic of Congo. The few reports from the Central African Republic have been limited to cases in the far South closely bordering the Congos. Team members of an international medical organisation have suspected clinically two human cases of MPX, associated with clinical signs of coagulopathy and haemorrhage in the North of the country. Read More

    Viral Skin Diseases.
    Prim Care 2015 Dec;42(4):517-67
    Center for Dermatology, Laser, and Cosmetic Surgery, Psoriasis Infusion and Treatment Center, 9892 Bustleton Avenue, Suite 204, Philadelphia, PA 19115, USA.
    In the vast world of skin diseases, viral skin disorders account for a significant percentage. Most viral skin diseases present with an exanthem (skin rash) and, oftentimes, an accompanying enanthem (lesions involving the mucosal membrane). In this article, the various viral skin diseases are explored, including viral childhood exanthems (measles, rubella, erythema infectiosum, and roseola), herpes viruses (herpes simplex virus, varicella zoster virus, Kaposi sarcoma herpes virus, viral zoonotic infections [orf, monkeypox, ebola, smallpox]), and several other viral skin diseases, such as human papilloma virus, hand, foot, and mouth disease, molluscum contagiosum, and Gianotti-Crosti syndrome. Read More

    EPIPOX: Immunoinformatic Characterization of the Shared T-Cell Epitome between Variola Virus and Related Pathogenic Orthopoxviruses.
    J Immunol Res 2015 28;2015:738020. Epub 2015 Oct 28.
    School of Medicine, Unit of Immunology, Complutense University of Madrid, Pza. Ramón y Cajal, s/n, 28040 Madrid, Spain.
    Concerns that variola viruses might be used as bioweapons have renewed the interest in developing new and safer smallpox vaccines. Variola virus genomes are now widely available, allowing computational characterization of the entire T-cell epitome and the use of such information to develop safe and yet effective vaccines. To this end, we identified 124 proteins shared between various species of pathogenic orthopoxviruses including variola minor and major, monkeypox, cowpox, and vaccinia viruses, and we targeted them for T-cell epitope prediction. Read More

    Comparison of the Cowpox Virus and Vaccinia Virus Mature Virion Proteome: Analysis of the Species- and Strain-Specific Proteome.
    PLoS One 2015 10;10(11):e0141527. Epub 2015 Nov 10.
    Centre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS1), Robert Koch Institute, Berlin, Germany.
    Cowpox virus (CPXV) causes most zoonotic orthopoxvirus (OPV) infections in Europe and Northern as well as Central Asia. The virus has the broadest host range of OPV and is transmitted to humans from rodents and other wild or domestic animals. Increasing numbers of human CPXV infections in a population with declining immunity have raised concerns about the virus' zoonotic potential. Read More

    Further Assessment of Monkeypox Virus Infection in Gambian Pouched Rats (Cricetomys gambianus) Using In Vivo Bioluminescent Imaging.
    PLoS Negl Trop Dis 2015 30;9(10):e0004130. Epub 2015 Oct 30.
    U.S. Geological Survey-National Wildlife Health Center, Madison, Wisconsin, United States of America.
    Monkeypox is a zoonosis clinically similar to smallpox in humans. Recent evidence has shown a potential risk of increased incidence in central Africa. Despite attempts to isolate the virus from wild rodents and other small mammals, no reservoir host has been identified. Read More

    Laboratory Investigations of African Pouched Rats (Cricetomys gambianus) as a Potential Reservoir Host Species for Monkeypox Virus.
    PLoS Negl Trop Dis 2015 30;9(10):e0004013. Epub 2015 Oct 30.
    Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
    Monkeypox is a zoonotic disease endemic to central and western Africa, where it is a major public health concern. Although Monkeypox virus (MPXV) and monkeypox disease in humans have been well characterized, little is known about its natural history, or its maintenance in animal populations of sylvatic reservoir(s). In 2003, several species of rodents imported from Ghana were involved in a monkeypox outbreak in the United States with individuals of three African rodent genera (Cricetomys, Graphiurus, Funisciurus) shown to be infected with MPXV. Read More

    Development of a High-Content Orthopoxvirus Infectivity and Neutralization Assays.
    PLoS One 2015 1;10(10):e0138836. Epub 2015 Oct 1.
    Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology (DHCPP), National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Centers for Disease Control and Prevention, Atlanta, Georgia, Unites States of America.
    Currently, a number of assays measure Orthopoxvirus neutralization with serum from individuals, vaccinated against smallpox. In addition to the traditional plaque reduction neutralization test (PRNT), newer higher throughput assays are based on neutralization of recombinant vaccinia virus, expressing reporter genes such as β-galactosidase or green fluorescent protein. These methods could not be used to evaluate neutralization of variola virus, since genetic manipulations of this virus are prohibited by international agreements. Read More

    A Multiplex PCR/LDR Assay for the Simultaneous Identification of Category A Infectious Pathogens: Agents of Viral Hemorrhagic Fever and Variola Virus.
    PLoS One 2015 18;10(9):e0138484. Epub 2015 Sep 18.
    Department of Medicine, Division of Infectious Diseases, Weill Medical College of Cornell University, New York, New York, United States of America; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, United States of America.
    CDC designated category A infectious agents pose a major risk to national security and require special action for public health preparedness. They include viruses that cause viral hemorrhagic fever (VHF) syndrome as well as variola virus, the agent of smallpox. VHF is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. Read More

    Comparison of Monkeypox Virus Clade Kinetics and Pathology within the Prairie Dog Animal Model Using a Serial Sacrifice Study Design.
    Biomed Res Int 2015 24;2015:965710. Epub 2015 Aug 24.
    Centers for Disease Control and Prevention, Poxvirus and Rabies Branch, Atlanta, GA 30333, USA.
    Monkeypox virus (MPXV) infection of the prairie dog is valuable to studying systemic orthopoxvirus disease. To further characterize differences in MPXV clade pathogenesis, groups of prairie dogs were intranasally infected (8 × 10(3) p.f. Read More

    Structural and Functional Characterization of Anti-A33 Antibodies Reveal a Potent Cross-Species Orthopoxviruses Neutralizer.
    PLoS Pathog 2015 Sep 1;11(9):e1005148. Epub 2015 Sep 1.
    Division of Cell Biology, La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America.
    Vaccinia virus A33 is an extracellular enveloped virus (EEV)-specific type II membrane glycoprotein that is essential for efficient EEV formation and long-range viral spread within the host. A33 is a target for neutralizing antibody responses against EEV. In this study, we produced seven murine anti-A33 monoclonal antibodies (MAbs) by immunizing mice with live VACV, followed by boosting with the soluble A33 homodimeric ectodomain. Read More

    Recent advances in the study of live attenuated cell-cultured smallpox vaccine LC16m8.
    Vaccine 2015 Nov 28;33(45):6106-11. Epub 2015 Aug 28.
    Department of Health Crisis Management, National Institute of Public Health, 2-3-6 Minami, Wako-shi, 351-0197, Saitama, Japan. Electronic address:
    LC16m8 is a live, attenuated, cell-cultured smallpox vaccine that was developed and licensed in Japan in the 1970s, but was not used in the campaign to eradicate smallpox. In the early 2000s, the potential threat of bioterrorism led to reconsideration of the need for a smallpox vaccine. Subsequently, LC16m8 production was restarted in Japan in 2002, requiring re-evaluation of its safety and efficacy. Read More

    Human Monkeypox in the Kivus, a Conflict Region of the Democratic Republic of the Congo.
    Am J Trop Med Hyg 2015 Oct 17;93(4):718-21. Epub 2015 Aug 17.
    Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia; Division Provinciale de la Santé, Ministère de la Santé Publique, Goma, Nord-Kivu, Democratic Republic of the Congo; Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic of the Congo; Ministère de la Santé Publique, Kinshasa, Democratic Republic of the Congo; U.S. Centers for Disease Control and Prevention, Kinshasa, Democratic Republic of the Congo; University of Kinshasa, Kinshasa, Democratic Republic of the Congo.
    Monkeypox (MPX) is a zoonotic Orthopoxvirus infection endemic in central and western Africa. Human MPX cases occur in the central and northern regions of the Democratic Republic of the Congo (DRC), and this is the first report of confirmed MPX cases in the forested areas of North and South Kivu Provinces, with a detailed epidemiological investigation for one case. The location of each case is within areas predicted to be suitable for MPX virus transmission based on an ecological niche model. Read More

    Evasion of the Innate Immune Type I Interferon System by Monkeypox Virus.
    J Virol 2015 Oct 5;89(20):10489-99. Epub 2015 Aug 5.
    School of Life Sciences, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA The Biodesign Institute, Center for Infectious Diseases and Vaccinology, Arizona State University, Tempe, Arizona, USA
    Unlabelled: The vaccinia virus (VACV) E3 protein has been shown to be important for blocking activation of the cellular innate immune system and allowing viral replication to occur unhindered. Mutation or deletion of E3L severely affects viral host range and pathogenesis. While the monkeypox virus (MPXV) genome encodes a homologue of the VACV E3 protein, encoded by the F3L gene, the MPXV gene is predicted to encode a protein with a truncation of 37 N-terminal amino acids. Read More

    Susceptibility of Marmosets (Callithrix jacchus) to Monkeypox Virus: A Low Dose Prospective Model for Monkeypox and Smallpox Disease.
    PLoS One 2015 6;10(7):e0131742. Epub 2015 Jul 6.
    Integrated Research Facility, National Institute of Allergy and Infectious Diseases, Fort Detrick, Maryland, United States of America.
    Although current nonhuman primate models of monkeypox and smallpox diseases provide some insight into disease pathogenesis, they require a high titer inoculum, use an unnatural route of infection, and/or do not accurately represent the entire disease course. This is a concern when developing smallpox and/or monkeypox countermeasures or trying to understand host pathogen relationships. In our studies, we altered half of the test system by using a New World nonhuman primate host, the common marmoset. Read More

    The effect of volume of interest definition on quantification of lymph node immune response to a monkeypox virus infection assessed by (18)F-FDG-PET.
    EJNMMI Res 2014 Dec 16;4(1):49. Epub 2014 Sep 16.
    Division of Clinical Research, Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 8200 Research Plaza, Frederick, MD, 21702, USA,
    Background: 2-deoxy-2-[(18)F]fluoro-D-glucose-positron emission tomography ((18)F-FDG-PET) is applied in the clinic for infection assessment and is under consideration for investigating the inflammatory/immune response in lymphoid tissue in animal models of viral infection. Assessing changes in (18)F-FDG uptake of lymph nodes (LNs), primary lymphoid tissues targeted during viral infection, requires suitable methods for image analysis. Similar to tumor evaluation, reliable quantitation of the LN function via multiple (18)F-FDG-PET sessions will depend how the volume of interest is defined. Read More

    BoHV-4-Based Vector Single Heterologous Antigen Delivery Protects STAT1(-/-) Mice from Monkeypoxvirus Lethal Challenge.
    PLoS Negl Trop Dis 2015 Jun 18;9(6):e0003850. Epub 2015 Jun 18.
    Department of Medical-Veterinary Science, University of Parma, Parma, Italy.
    Monkeypox virus (MPXV) is the etiological agent of human (MPX). It is an emerging orthopoxvirus zoonosis in the tropical rain forest of Africa and is endemic in the Congo-basin and sporadic in West Africa; it remains a tropical neglected disease of persons in impoverished rural areas. Interaction of the human population with wildlife increases human infection with MPX virus (MPXV), and infection from human to human is possible. Read More

    Poxvirus countermeasures during an emergency in the United States.
    Disaster Med Public Health Prep 2015 Apr;9(2):121-6
    Although smallpox was eradicated worldwide by 1980, national security experts remain concerned that it could be used in a deliberate attack. The United States and other governments have given priority to developing and stockpiling vaccines and antivirals to protect their populations from the potential reintroduction of this deadly disease. Public health officials are also concerned about the spread of related zoonotic orthopoxviruses such as monkeypox and cowpox, against which smallpox vaccine provides protection. Read More

    Introduction of Monkeypox into a Community and Household: Risk Factors and Zoonotic Reservoirs in the Democratic Republic of the Congo.
    Am J Trop Med Hyg 2015 Aug 26;93(2):410-5. Epub 2015 May 26.
    U.S. Centers for Disease Control and Prevention, Bacterial Special Pathogens Branch, Atlanta, Georgia; U.S. Centers for Disease Control and Prevention, Epidemic Intelligence Service, Atlanta, Georgia; U.S. Centers for Disease Control and Prevention, Poxvirus and Rabies Branch, Atlanta, Georgia; Minstere de la Santé, Kinshasa, The Democratic Republic of Congo; U.S. Centers for Disease Control and Prevention, Field Epidemiology Training Program, Kinshasa, The Democratic Republic of Congo; National Institute for Biomedical Research, Kinshasa, The Democratic Republic of Congo; U.S. Centers for Disease Control and Prevention Kinshasa, The Democratic Republic of Congo; University of Kinshasa, Department of Biology, Kinshasa, The Democratic Republic of Congo; Minstere de la Santé, Tshuapa Health District, The Democratic Republic of Congo; Kinshasa School of Public Health, The Democratic Republic of Congo.
    An increased incidence of monkeypox (MPX) infections in the Democratic Republic of the Congo was noted by the regional surveillance system in October 2013. Little information exists regarding how MPX is introduced into the community and the factors associated with transmission within the household. Sixty-eight wild animals were collected and tested for Orthopoxvirus. Read More

    Using the Ground Squirrel (Marmota bobak) as an Animal Model to Assess Monkeypox Drug Efficacy.
    Transbound Emerg Dis 2017 Feb 5;64(1):226-236. Epub 2015 May 5.
    Federal Budgetary Research Institution - State Research Center of Virology and Biotechnology VECTOR, Federal Service for Surveillance on Consumer Rights Protection and Human Well-being, Koltsovo, Russia.
    In experiments to study the sensitivity of ground squirrels (Marmota bobak) to monkeypox virus (MPXV) at intranasal challenge, expressed pox-like clinical symptoms (hyperthermia, lymphadenitis, skin rash all over the body and mucous membranes and others) were observed 7-9 days post-infection. The 50% infective dose (ID50 ) of MPXV for these marmots determined by the presence of clinical signs of the disease was 2.2 log10 PFU. Read More

    Collection and Utilization of Animal Carcasses Associated with zoonotic Disease in Tshuapa District, the Democratic Republic of the Congo, 2012.
    J Wildl Dis 2015 Jul 1;51(3):734-8. Epub 2015 May 1.
    1  Poxvirus and Rabies Program, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Mailstop A-30, 1600 Clifton Road, Atlanta Georgia, USA.
    The collection and consumption of animal carcasses is a common activity in forested areas of the Congo River basin and creates sustainability, conservation, and health concerns. Residents of the Tshuapa District reported collecting the remains of 5,878 animals from >30 species when surveyed about their wildlife consumption habits. Carcasses were discovered in varying degrees of decomposition and were often consumed at home or sold in local markets. Read More

    A phylogeographic investigation of African monkeypox.
    Viruses 2015 Apr 22;7(4):2168-84. Epub 2015 Apr 22.
    Poxvirus and Rabies Branch, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, Atlanta, GA 30333, USA.
    Monkeypox is a zoonotic disease caused by a virus member of the genus Orthopoxvirus and is endemic to Central and Western African countries. Previous work has identified two geographically disjuct clades of monkeypox virus based on the analysis of a few genomes coupled with epidemiological and clinical analyses; however, environmental and geographic causes of this differentiation have not been explored. Here, we expand previous phylogenetic studies by analyzing a larger set of monkeypox virus genomes originating throughout Sub-Saharan Africa to identify possible biogeographic barriers associated with genetic differentiation; and projected ecological niche models onto environmental conditions at three periods in the past to explore the potential role of climate oscillations in the evolution of the two primary clades. Read More

    Treatment with the smallpox antiviral tecovirimat (ST-246) alone or in combination with ACAM2000 vaccination is effective as a postsymptomatic therapy for monkeypox virus infection.
    Antimicrob Agents Chemother 2015 Jul 20;59(7):4296-300. Epub 2015 Apr 20.
    SIGA Technologies, Inc., Corvallis, Oregon, USA.
    The therapeutic efficacies of smallpox vaccine ACAM2000 and antiviral tecovirimat given alone or in combination starting on day 3 postinfection were compared in a cynomolgus macaque model of lethal monkeypox virus infection. Postexposure administration of ACAM2000 alone did not provide any protection against severe monkeypox disease or mortality. In contrast, postexposure treatment with tecovirimat alone or in combination with ACAM2000 provided full protection. Read More

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