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https://www.readbyqxmd.com/read/28104453/alphavirus-polymerase-and-rna-replication
#1
REVIEW
Maija K Pietilä, Kirsi Hellström, Tero Ahola
Alphaviruses are typically arthropod-borne, and many are important pathogens such as chikungunya virus. Alphaviruses encode four nonstructural proteins (nsP1-4), initially produced as a polyprotein P1234. nsP4 is the core RNA-dependent RNA polymerase but all four nsPs are required for RNA synthesis. The early replication complex (RC) formed by the polyprotein P123 and nsP4 synthesizes minus RNA strands, and the late RC composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus strands...
January 16, 2017: Virus Research
https://www.readbyqxmd.com/read/28092259/-first-case-of-chikungunya-fever-in-hermosillo-sonora-mexico
#2
Miguel Ángel Martínez-Medina, Ismael Antonio Cañedo-Dorame
The Chikungunya is an arbovirus first described during a 1952 outbreak of febrile exantematic disease in southern Tanganyika (now Tanzania). It is a virus within the alphavirus genus of the Togaviridae family, it is usually transmitted to humans by Aedes mosquitoes. Typically, the disease manifests as acute onset of fever and joint pains. This study describes the clinical characteristics the first imported case infected with chikungunya fever (CHIK) in Hermosillo, Sonora, Mexico. We report the case of a 30 years old man seen in our emergency department due to fever, polyarthralgia, rash and headache...
January 2017: Revista Médica del Instituto Mexicano del Seguro Social
https://www.readbyqxmd.com/read/28075229/altered-mitochondrial-dynamics-as-a-consequence-of-venezuelan-equine-encephalitis-virus-infection
#3
Forrest Keck, Taryn Brooks-Faulconer, Tyler Lark, Pavitra Ravishankar, Charles Bailey, Carolina Salvador-Morales, Aarthi Narayanan
Mitochondria are sentinel organelles that are impacted by various forms of cellular stress, including viral infections. While signaling events associated with mitochondria, including those activated by pathogen associated molecular patterns (PAMPs), are widely studied, alterations in mitochondrial distribution and changes in mitochondrial dynamics are also beginning to be associated with cellular insult. Cells of neuronal origin have been demonstrated to display remarkable alterations in several instances, including neurodegenerative disorders...
January 11, 2017: Virulence
https://www.readbyqxmd.com/read/28060952/trim25-enhances-the-antiviral-action-of-zinc-finger-antiviral-protein-zap
#4
Melody M H Li, Zerlina Lau, Pamela Cheung, Eduardo G Aguilar, William M Schneider, Leonia Bozzacco, Henrik Molina, Eugen Buehler, Akinori Takaoka, Charles M Rice, Dan P Felsenfeld, Margaret R MacDonald
The host factor and interferon (IFN)-stimulated gene (ISG) product, zinc-finger antiviral protein (ZAP), inhibits a number of diverse viruses by usurping and intersecting with multiple cellular pathways. To elucidate its antiviral mechanism, we perform a loss-of-function genome-wide RNAi screen to identify cellular cofactors required for ZAP antiviral activity against the prototype alphavirus, Sindbis virus (SINV). In order to exclude off-target effects, we carry out stringent confirmatory assays to verify the top hits...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28030537/molecular-virologic-and-clinical-characteristics-of-a-chikungunya-fever-outbreak-in-la-romana-dominican-republic-2014
#5
Rose M Langsjoen, Rebecca J Rubinstein, Tiffany F Kautz, Albert J Auguste, Jesse H Erasmus, Liddy Kiaty-Figueroa, Renessa Gerhardt, David Lin, Kumar L Hari, Ravi Jain, Nicolas Ruiz, Antonio E Muruato, Jael Silfa, Franklin Bido, Matthew Dacso, Scott C Weaver
Since emerging in Saint Martin in 2013, chikungunya virus (CHIKV), an alphavirus transmitted by the Aedes aegypti mosquito, has infected approximately two million individuals in the Americas, with over 500,000 reported cases in the Dominican Republic (DR). CHIKV-infected patients typically present with a febrile syndrome including polyarthritis/polyarthralgia, and a macropapular rash, similar to those infected with dengue and Zika viruses, and malaria. Nevertheless, many Dominican cases are unconfirmed due to the unavailability and high cost of laboratory testing and the absence of specific treatment for CHIKV infection...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28005523/discovery-of-a-novel-alphavirus-related-to-eilat-virus
#6
Kyra Hermanns, Florian Zirkel, Anne Kopp, Marco Marklewitz, Innocent Rwego, Alejandro Estrada, Thomas Robert Gillespie, Christian Drosten, Sandra Junglen
Most alphaviruses are transmitted by arthropods and infect vertebrate hosts. An exception is Eilat virus (EILV), the only described alphavirus with a host range restricted to insects. We established a new generic reverse transcription PCR assay for alphaviruses and tested 8,860 tropical mosquitoes. We detected a novel alphavirus, tentatively named Taï Forest alphavirus (TALV), in Culex decens mosquitoes collected in Côte d'Ivoire. The full genome was sequenced and closest similarity was found to EILV. Pairwise amino acid identities to EILV ranged between 67-88% for the corresponding proteins suggesting that TALV defines a proposed new alphavirus species...
December 21, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/28001232/a-case-of-chikungunya-virus-disease-presenting-with-remarkable-acute-arthritis-of-a-previously-damaged-finger-joint
#7
Walter de Araujo Eyer-Silva, Henrique de Barros Pinto, Guilherme Almeida Rosa da Silva, Fernando Raphael de Almeida Ferry
Chikungunya virus (CHIKV) is a mosquito-borne arthritogenic alphavirus that has recently been introduced to Brazil. We report the case of a 36-year-old male patient from the City of Rio de Janeiro who developed molecularly-confirmed CHIKV disease and whose clinical picture was remarkable because of acute arthritis of an interphalangeal joint that had been damaged by trauma 8 years previously. This case illustrates that acute CHIKV disease may preferentially target previously damaged joints. Careful study of individual cases may provide valuable information on the presentation and management of this emerging zoonosis in Brazil...
November 2016: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/27997927/correction-a-prime-boost-vaccination-strategy-in-cattle-to-prevent-foot-and-mouth-disease-using-a-single-cycle-alphavirus-vector-and-empty-capsid-particles
#8
(no author information available yet)
[This corrects the article DOI: 10.1371/journal.pone.0157435.].
2016: PloS One
https://www.readbyqxmd.com/read/27995422/entry-of-severe-fever-with-thrombocytopenia-syndrome-virus
#9
REVIEW
Fei Yuan, Aihua Zheng
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a globe-shaped virus covered by a dense icosahedral array of glycoproteins Gn/Gc that mediate the attachment of the virus to host cells and the fusion of viral and cellular membranes. Several membrane factors are involved in virus entry, including C-type lectins and nonmuscle myosin heavy chain IIA. The post-fusion crystal structure of the Gc protein suggests that it is a class II membrane fusion protein, similar to the E/E1 protein of flaviviruses and alphaviruses...
December 16, 2016: Virologica Sinica
https://www.readbyqxmd.com/read/27993855/obatoclax-inhibits-alphavirus-membrane-fusion-by-neutralizing-the-acidic-environment-of-endocytic-compartments
#10
Finny S Varghese, Kai Rausalu, Marika Hakanen, Sirle Saul, Beate M Kümmerer, Petri Susi, Andres Merits, Tero Ahola
As new pathogenic viruses continue to emerge, it is paramount to have intervention strategies that target a common denominator in these pathogens. The fusion of viral and cellular membranes during viral entry is one such process that is used by many pathogenic viruses including chikungunya virus, West Nile virus, influenza virus etc. Obatoclax, a small-molecule antagonist of the Bcl-2 family of proteins was previously determined to be antiviral against influenza A virus and also Sindbis virus. Here, we report it to be active against alphaviruses like chikungunya virus (EC50 = 0...
December 19, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27991917/a-chikungunya-fever-vaccine-utilizing-an-insect-specific-virus-platform
#11
Jesse H Erasmus, Albert J Auguste, Jason T Kaelber, Huanle Luo, Shannan L Rossi, Karla Fenton, Grace Leal, Dal Y Kim, Wah Chiu, Tian Wang, Ilya Frolov, Farooq Nasar, Scott C Weaver
Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to inactivated vaccines. In contrast, the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters. To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform. To address the chikungunya fever (CHIKF) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the chikungunya virus (CHIKV) structural proteins...
December 19, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27977778/intercellular-extensions-are-induced-by-the-alphavirus-structural-proteins-and-mediate-virus-transmission
#12
Maria Guadalupe Martinez, Margaret Kielian
Alphaviruses are highly organized enveloped RNA viruses with an internal nucleocapsid surrounded by a membrane containing the E2 and E1 transmembrane proteins. Alphavirus budding takes place at the plasma membrane and requires the interaction of the cytoplasmic domain of E2 with the capsid protein. Here we used WT alphaviruses and Sindbis virus in which E2 was fused to a fluorescent protein to characterize virus exit from host cells. Our results show that alphavirus infection induced striking modifications of the host cell cytoskeleton and resulted in the formation of stable intercellular extensions that emanated exclusively from the infected cell...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27920182/monoclonal-antibodies-as-prophylactic-and-therapeutic-agents-against-chikungunya-virus
#13
April M Clayton
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is responsible for considerable epidemics worldwide and recently emerged in the Americas in 2013. CHIKV may cause long-lasting arthralgia after acute infection. With currently no licensed vaccines or antivirals, the design of effective therapies to prevent or treat CHIKV infection is of utmost importance and will be facilitated by increased understanding of the dynamics of chikungunya. In this article, monoclonal antibodies against CHIKV as viable prophylactic and therapeutic agents will be discussed...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27920181/chikungunya-virus-vaccines-viral-vector-based-approaches
#14
Katrin Ramsauer, Frédéric Tangy
In 2013, a major chikungunya virus (CHIKV) epidemic reached the Americas. In the past 2 years, >1.7 million people have been infected. In light of the current epidemic, with millions of people in North and South America at risk, efforts to rapidly develop effective vaccines have increased. Here, we focus on CHIKV vaccines that use viral-vector technologies. This group of vaccine candidates shares an ability to potently induce humoral and cellular immune responses by use of highly attenuated and safe vaccine backbones...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27920178/animal-models-of-chikungunya-virus-infection-and-disease
#15
Nicole N Haese, Rebecca M Broeckel, David W Hawman, Mark T Heise, Thomas E Morrison, Daniel N Streblow
Chikungunya virus (CHIKV) is a reemerging alphavirus that causes acute febrile illness and severe joint pain in humans. Although acute symptoms often resolve within a few days, chronic joint and muscle pain can be long lasting. In the last decade, CHIKV has caused widespread outbreaks of unprecedented scale in the Americas, Asia, and the Indian Ocean island regions. Despite these outbreaks and the continued expansion of CHIKV into new areas, mechanisms of chikungunya pathogenesis and disease are not well understood...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27920171/chikungunya-pathogenesis-from-the-clinics-to-the-bench
#16
Philippe Gasque, Marie Christine Jaffar Bandjee, Marcela Mercado Reyes, Diego Viasus
Chikungunya alphavirus has caused large epidemics worldwide and leads to acute incapacitating polyarthralgia. The inflammatory reaction over several days will drive robust innate and humoral responses essential to control the infection. Critically, fatal cases and mother-to-child transmission have also been described. Chikungunya can give rise to chronic musculoskeletal diseases, which can last for months to years, particularly in elderly individuals, and occasionally leads to seronegative rheumatoid arthritis-like pathologies...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27919709/evaluation-of-anti-zika-virus-activities-of-broad-spectrum-antivirals-and-nih-clinical-collection-compounds-using-a-cell-based-high-throughput-screen-assay
#17
Robert S Adcock, Yong-Kyu Chu, Jennifer E Golden, Dong-Hoon Chung
Recent studies have clearly underscored the association between Zika virus (ZIKV) and severe neurological diseases such as microcephaly and Guillain-Barre syndrome. Given the historical complacency surrounding this virus, however, no significant antiviral screenings have been performed to specifically target ZIKV. As a result, there is an urgent need for a validated screening method and strategy that is focused on highlighting potential anti-ZIKV inhibitors that can be further advanced via rigorous validation and optimization...
February 2017: Antiviral Research
https://www.readbyqxmd.com/read/27905123/selective-precipitation-reaction-a-novel-diagnostic-test-for-tissue-pathology-in-atlantic-salmon-salmo-salar-infected-with-salmonid-alphavirus-sav3
#18
M Braceland, J Tinsley, D Cockerill, R Bickerdike, M F McLoughlin, P D Eckersall
While investigating biomarkers for infection with salmonid alphavirus (SAV), the cause of pancreas disease (PD), a selective precipitation reaction (SPR) has been discovered in serum which could be an on-farm qualitative test and an in-laboratory quantitative assay for health assessments in aquaculture. Mixing serum from Atlantic salmon, Salmo salar, with SAV infection with a sodium acetate buffer caused a visible precipitation which does not occur with serum from healthy salmon. Proteomic examination of the precipitate has revealed that the components are a mix of muscle proteins, for example enolase and aldolase, along with serum protein such as serotransferrin and complement C9...
November 30, 2016: Journal of Fish Diseases
https://www.readbyqxmd.com/read/27902702/selective-inhibitor-of-nuclear-export-sine-compounds-alter-new-world-alphavirus-capsid-localization-and-reduce-viral-replication-in-mammalian-cells
#19
Lindsay Lundberg, Chelsea Pinkham, Cynthia de la Fuente, Ashwini Brahms, Nazly Shafagati, Kylie M Wagstaff, David A Jans, Sharon Tamir, Kylene Kehn-Hall
The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27901124/analysis-of-chikungunya-virus-proteins-reveals-that-non-structural-proteins-nsp2-and-nsp3-exhibit-rna-interference-rnai-suppressor-activity
#20
Kalika Mathur, Abhishek Anand, Sunil Kumar Dubey, Neeti Sanan-Mishra, Raj K Bhatnagar, Sujatha Sunil
RNAi pathway is an antiviral defence mechanism employed by insects that result in degradation of viral RNA thereby curbing infection. Several viruses including flaviviruses encode viral suppressors of RNAi (VSRs) to counteract the antiviral RNAi pathway. Till date, no VSR has been reported in alphaviruses. The present study was undertaken to evaluate chikungunya virus (CHIKV) proteins for RNAi suppressor activity. We systematically analyzed all nine CHIKV proteins for RNAi suppressor activity using Sf21 RNAi sensor cell line based assay...
November 30, 2016: Scientific Reports
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