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Yu-Ming Wang, Jeng-Wei Lu, Chang-Chi Lin, Yuan-Fan Chin, Tzong-Yuan Wu, Liang-In Lin, Zheng-Zong Lai, Szu-Cheng Kuo, Yi-Jung Ho
Chikungunya disease results from an infection with the arbovirus, chikungunya virus (CHIKV). Symptoms of CHIKV include fever and persistent, severe arthritis. In recent years, several antiviral drugs have been evaluated in clinical trials; however, no registered antivirals have been approved for clinical therapy. In this study, we established a high-throughput screening (HTS) system based on CHIKV 26S mediated insect cell fusion inhibition assay. Our screening system was able to search potential anti-CHIKV drugs in vitro...
October 11, 2016: Antiviral Research
Pratyush Kumar Das, Laura Puusepp, Finny S Varghese, Age Utt, Tero Ahola, Dzmitry G Kananovich, Margus Lopp, Andres Merits, Mati Karelson
Chikungunya virus (CHIKV, genus Alphavirus) is the causative agent of chikungunya fever. CHIKV replication can be inhibited by some broad-spectrum antiviral compounds; in contrast there is very little information about compounds specifically inhibiting the enzymatic activities of CHIKV replication proteins. These proteins are translated in the form of a nonstructural (ns) P1234 polyprotein precursor from the CHIKV positive-strand RNA genome. Active forms of replicase enzymes are generated using the autoproteolytic activity of nsP2...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Anika Bartholomäus, Daniel Wibberg, Anika Winkler, Alfred Pühler, Andreas Schlüter, Mark Varrelmann
The complete genome of a novel mycovirus, named Rhizoctonia solani flexivirus 1 (RsFV-1), which infects an avirulent strain of Rhizoctonia solani AG 2-2 IV, was sequenced and analyzed. Its RNA genome consists of 10,621 nucleotides, excluding the poly-A tail, and encodes a single protein of 3477 amino acids. The identification of conserved motifs of methyltransferase, helicase and RNA-dependent RNA polymerase revealed its relatedness to members of the alphavirus-like superfamily of positive-strand RNA viruses...
October 12, 2016: Archives of Virology
Aileen E O'Hearn, Matthew A Voorhees, David P Fetterer, Nadia Wauquier, Moinya R Coomber, James Bangura, Joseph N Fair, Jean-Paul Gonzalez, Randal J Schoepp
BACKGROUND: Sub-Saharan Africa is home to a variety of pathogens, but disease surveillance and the healthcare infrastructure necessary for proper management and control are severely limited. Lassa virus, the cause of Lassa fever, a severe hemorrhagic fever in humans is endemic in West Africa. In Sierra Leone at the Kenema Government Hospital Lassa Diagnostic Laboratory, up to 70 % of acute patient samples suspected of Lassa fever test negative for Lassa virus infection. This large amount of acute undiagnosed febrile illness can be attributed in part to an array of hemorrhagic fever and arthropod-borne viruses causing disease that goes undetected and untreated...
October 3, 2016: Virology Journal
Richard Hoyos-López, Juan Suaza-Vasco, Guillermo Rúa-Uribe, Sandra Uribe, Juan Carlos Gallego-Gómez
Arboviruses belonging to the genera Flavivirus and Alphavirus were detected in mosquitoes in a rural area of San Bernardo del Viento (Córdoba, Colombia). A total of 22,180 mosquitoes were collected, sorted into 2,102 pools, and tested by generic/nested reverse transcription-polymerase chain reaction. Venezuelan equine encephalitis virus, dengue virus, West Nile virus, St. Louis encephalitis virus, yellow fever virus, and Culex flavivirus were detected and identified by sequencing. The detection of arboviral pathogens in this zone represents possible circulation and indicates a human health risk, demonstrating the importance of virological surveillance activities...
October 3, 2016: Memórias do Instituto Oswaldo Cruz
Pranav Patel, Ahmed Abd El Wahed, Oumar Faye, Pauline Prüger, Marco Kaiser, Sasikanya Thaloengsok, Sukathida Ubol, Anavaj Sakuntabhai, Isabelle Leparc-Goffart, Frank T Hufert, Amadou A Sall, Manfred Weidmann, Matthias Niedrig
BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. METHODOLOGY/PRINCIPAL FINDINGS: In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed...
September 2016: PLoS Neglected Tropical Diseases
Diane E Griffin, Victoria K Baxter
Infection of mice with Sindbis virus (SINV) produces encephalomyelitis and provides a model for examination of the central nervous system (CNS) immune response to alphavirus infection. Clearance of infectious virus is accomplished through a cooperative effort between SINV-specific antibody and interferon gamma (IFN-γ), but the regulatory interactions are poorly understood. To determine the effects of IFN-γ on clinical disease and the antiviral immune response, C57BL/6 mice lacking IFN-γ (Ifng-/-) or IFN-γ receptor (Ifngr1-/-) were studied in comparison to wild-type (WT) mice...
September 22, 2016: Journal of General Virology
Pascale Krejbich-Trotot, Essia Belarbi, Miora Ralambondrainy, Chaker El-Kalamouni, Wildriss Viranaicken, Pierre Roques, Philippe Desprès, Gilles Gadea
Alphaviruses such as Chikungunya and Ross River (RRV) viruses are associated with persistent arthritis and arthralgia in humans. Monocytes and macrophages are believed to play an important role in alphaviral arthritides. In this study, we evaluated RRV permissiveness of the human acute leukemia MM6 cell line. Viral growth analysis showed that RRV infection of MM6 cells resulted in a very low virus progeny production with daily output. Using recombinant RRV expressing the reporter gene Renilla luciferase, a weak viral replication level was detected in infected cells at the early stages of infection...
October 2, 2016: Virus Research
Jelena Vasilevska, Gustavo Antonio De Souza, Maria Stensland, Dace Skrastina, Dmitry Zhulenvovs, Raimonds Paplausks, Baiba Kurena, Tatjana Kozlovska, Anna Zajakina
Alphavirus vectors are promising tools for cancer treatment. However, relevant entry mechanisms and interactions with host cells are still not clearly understood. The first step toward a more effective therapy is the identification of novel intracellular alterations that could be associated with cancer aggressiveness and could affect the therapeutic potential of these vectors. In this study, we observed that alphaviruses efficiently infected B16 mouse melanoma tumors/tumor cells in vivo, whereas their transduction efficiency in B16 cells under in vitro conditions was blocked...
August 11, 2016: Cancer Biology & Therapy
Amber B Rico, Aaron T Phillips, Tony Schountz, Donald L Jarvis, Ronald B Tjalkens, Ann M Powers, Ken E Olson
Eastern, Venezuelan and western equine encephalitis viruses (EEEV, VEEV, and WEEV) are mosquito-borne viruses that cause substantial disease in humans and other vertebrates. Vaccines are limited and current treatment options have not proven successful. In this report, we vaccinated outbred mice with lipid-antigen-nucleic acid-complexes (LANACs) containing VEEV E1+WEEV E1 antigen and characterized protective efficacy against lethal EEEV, VEEV, and WEEV challenge. Vaccination resulted in complete protection against EEEV, VEEV, and WEEV in CD-1 mice...
September 12, 2016: Virology
Mariana G Cavalheiro, Leandro Silva DA Costa, Holmes S Campos, Letícia S Alves, Iranaia Assunção-Miranda, Andrea T DA Poian
Alphaviruses among the viruses that cause arthritis, consisting in a public health problem worldwide by causing localized outbreaks, as well as large epidemics in humans. Interestingly, while the Old World alphaviruses are arthritogenic, the New World alphaviruses cause encephalitis. One exception is Mayaro virus (MAYV), which circulates exclusively in South America but causes arthralgia and is phylogenetically related to the Old World alphaviruses. Although MAYV-induced arthritis in humans is well documented, the molecular and cellular factors that contribute to its pathogenesis are completely unknown...
September 2016: Anais da Academia Brasileira de Ciências
Rajesh Sharma, Benazir Fatma, Amrita Saha, Sailesh Bajpai, Srinivas Sistla, Paban Kumar Dash, Manmohan Parida, Pravindra Kumar, Shailly Tomar
The protein-protein interactions (PPIs) of the transmembrane glycoprotein E2 with the hydrophobic pocket on the surface of capsid protein (CP) plays a critical role in alphavirus life cycle. Dioxane based derivatives targeting PPIs have been reported to possess antiviral activity against Sindbis Virus (SINV), the prototype alphavirus. In this study, the binding of picolinic acid (PCA) to the conserved hydrophobic pocket of capsid protein was analyzed by molecular docking, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and fluorescence spectroscopy...
November 2016: Virology
Xinlu Wang, Melody M H Li, Jing Zhao, Shenglan Li, Margaret R MacDonald, Charles M Rice, Xiang Gao, Guangxia Gao
: Viral infection induces production of type I interferons (IFNs), which stimulate the expression of a variety of antiviral factors to inhibit viral replication. To establish effective infection, viruses need to develop strategies to evade the immune responses. A neurovirulent Sindbis virus strain with neuroinvasive properties (SVNI) causes lethal encephalitis in mice, and its replication in cultured cells is inhibited by the zinc-finger antiviral protein (ZAP), a host factor that specifically inhibits the replication of certain viruses by binding to the viral mRNAs and repressing the translation and promoting the degradation of target mRNA...
August 31, 2016: Journal of Virology
Lisa Henß, Simon Beck, Tatjana Weidner, Nadine Biedenkopf, Katja Sliva, Christopher Weber, Stephan Becker, Barbara S Schnierle
BACKGROUND: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes high fever, rash, and recurrent arthritis in humans. It has efficiently adapted to Aedes albopictus, which also inhabits temperate regions and currently causes large outbreaks in the Caribbean and Latin America. Ebola virus (EBOV) is a member of the filovirus family. It causes the Ebola virus disease (EDV), formerly known as Ebola hemorrhagic fever in humans and has a mortality rate of up to 70 %. The last outbreak in Western Africa was the largest in history and has caused approximately 25,000 cases and 10,000 deaths...
2016: Virology Journal
Szu-Cheng Kuo, Yu-Ming Wang, Yi-Jung Ho, Tein-Yao Chang, Zheng-Zong Lai, Pei-Yi Tsui, Tzong-Yuan Wu, Chang-Chi Lin
The chikungunya virus (CHIKV), an arthritogenic alphavirus, has caused explosive epidemics involving millions of cases. Globally expanding pandemics involving CHIKV and post-CHIKV rheumatic disorders are increasing public health concerns. However, no antiviral interventions or vaccines to control CHIKV infection have yet been approved. Although suramin has been possess anti-CHIKV activity in vitro, whether suramin has anti-CHIKV activity in vivo remains unknown. This study aimed to determine whether suramin treatment could ameliorate CHIKV-induced arthritis in a C57BL/6 mice model...
October 2016: Antiviral Research
Pennelope K Blakely, Amanda K Huber, David N Irani
BACKGROUND: Alphaviruses can cause fatal encephalitis in humans. Natural infections occur via the bite of infected mosquitos, but aerosol transmissibility makes some of these viruses potential bioterrorism agents. Central nervous system (CNS) host responses contribute to alphavirus pathogenesis in experimental models and are logical therapeutic targets. We investigated whether reactive oxygen species (ROS) generated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity within the CNS contributes to fatal alphavirus encephalitis in mice...
2016: Journal of Neuroinflammation
Marilia Farignoli Romeiro, William Marciel de Souza, Aline Lavado Tolardo, Luiz Carlos Vieira, Dyana Alves Henriques, Jansen de Araujo, Carlos Eduardo Hassegawa Siqueira, Tatiana Elias Colombo, Victor Hugo Aquino, Benedito Antonio Lopes da Fonseca, Roberta Vieira de Morais Bronzoni, Maurício Lacerda Nogueira, Edison Luiz Durigon, Luiz Tadeu Moraes Figueiredo
Mosquito-borne alphaviruses are widely distributed throughout the world, causing important human illnesses. Therefore, the development of methods to enable early diagnosis of infections by alphavirus is essential. We show here the development and evaluation of a quantitative real-time RT-PCR using genus-specific primers to the nsP1 viral gene of all mosquito-borne alphaviruses. The specificity and sensitivity of the assay were tested using seven alphaviruses and RNA transcribed from Venezuelan equine encephalitis virus...
November 2016: Archives of Virology
L Delang, C Li, A Tas, G Quérat, I C Albulescu, T De Burghgraeve, N A Segura Guerrero, A Gigante, G Piorkowski, E Decroly, D Jochmans, B Canard, E J Snijder, M J Pérez-Pérez, M J van Hemert, B Coutard, P Leyssen, J Neyts
The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. We discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected and these carried a P34S substitution in non-structural protein 1 (nsP1), the main enzyme involved in alphavirus RNA capping...
2016: Scientific Reports
Finny S Varghese, Bastian Thaa, Siti Naqiah Amrun, Diane Simarmata, Kai Rausalu, Tuula A Nyman, Andres Merits, Gerald M McInerney, Lisa F P Ng, Tero Ahola
: Chikungunya virus (CHIKV) has infected millions of people in the tropical and subtropical regions since its reemergence in the last decade. We recently identified the nontoxic plant alkaloid berberine as an antiviral substance against CHIKV in a high-throughput screen. Here, we show that berberine is effective in multiple cell types against a variety of CHIKV strains, also at a high multiplicity of infection, consolidating the potential of berberine as an antiviral drug. We excluded any effect of this compound on virus entry or on the activity of the viral replicase...
November 1, 2016: Journal of Virology
Chia-Jung Chang, Iris Jenssen, Børre Robertsen
Salmonid alphavirus 3 (SAV3) causes pancreas disease (PD), which is a major problem in Norwegian aquaculture of Atlantic salmon. In this work we studied antiviral activities of salmon type I interferons IFNa, IFNb and IFNc against SAV3 infection in cell culture and in live fish to increase the understanding of the innate immunity of salmon against this virus. Recombinant IFNa, IFNb and IFNc all induced antiviral activity against SAV3 in ASK cells. For in vivo studies, we injected salmon presmolts intramuscularly with plasmids encoding salmon IFNa, IFNb and IFNc or a control plasmid and measured expression of the antiviral protein Mx in pancreas after 2 and 10 weeks and protection against SAV3 infection after 10 weeks...
October 2016: Fish & Shellfish Immunology
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