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https://www.readbyqxmd.com/read/29138302/disruption-of-the-opal-stop-codon-attenuates-chikungunya-virus-induced-arthritis-and-pathology
#1
Jennifer E Jones, Kristin M Long, Alan C Whitmore, Wes Sanders, Lance R Thurlow, Julia A Brown, Clayton R Morrison, Heather Vincent, Kayla M Peck, Christian Browning, Nathaniel Moorman, Jean K Lim, Mark T Heise
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus responsible for several significant outbreaks of debilitating acute and chronic arthritis and arthralgia over the past decade. These include a recent outbreak in the Caribbean islands and the Americas that caused more than 1 million cases of viral arthralgia. Despite the major impact of CHIKV on global health, viral determinants that promote CHIKV-induced disease are incompletely understood. Most CHIKV strains contain a conserved opal stop codon at the end of the viral nsP3 gene...
November 14, 2017: MBio
https://www.readbyqxmd.com/read/29114027/an-alphavirus-e2-membrane-proximal-domain-promotes-envelope-protein-lateral-interactions-and-virus-budding
#2
Emily A Byrd, Margaret Kielian
Alphaviruses are members of a group of small enveloped RNA viruses that includes important human pathogens such as Chikungunya virus and the equine encephalitis viruses. The virus membrane is covered by a lattice composed of 80 spikes, each a trimer of heterodimers of the E2 and E1 transmembrane proteins. During virus endocytic entry, the E1 glycoprotein mediates the low-pH-dependent fusion of the virus membrane with the endosome membrane, thus initiating virus infection. While much is known about E1 structural rearrangements during membrane fusion, it is unclear how the E1/E2 dimer dissociates, a step required for the fusion reaction...
November 7, 2017: MBio
https://www.readbyqxmd.com/read/29091706/neutralizing-antibodies-for-orthobunyaviruses-in-pantanal-brazil
#3
Alex Pauvolid-Corrêa, Zilca Campos, Raquel Soares, Rita Maria Ribeiro Nogueira, Nicholas Komar
The Pantanal is a hotspot for arbovirus studies in South America. Various medically important flaviviruses and alphaviruses have been reported in domestic and wild animals in the region. To expand the knowledge of local arbovirus circulation, a serosurvey for 14 Brazilian orthobunyaviruses was conducted with equines, sheep and free-ranging caimans. Sera were tested for specific viral antibodies using plaque-reduction neutralization test (PRNT). Monotypic reactions were detected for Maguari, Xingu, Apeu, Guaroa, Murutucu, Oriboca, Oropouche and Nepuyo viruses...
November 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29084215/complex-antigen-presentation-pathway-for-an-hla-a-0201-restricted-epitope-from-chikungunya-6k-protein
#4
Elena Lorente, Alejandro Barriga, Juan García-Arriaza, François A Lemonnier, Mariano Esteban, Daniel López
BACKGROUND: The adaptive cytotoxic T lymphocyte (CTL)-mediated immune response is critical for clearance of many viral infections. These CTL recognize naturally processed short viral antigenic peptides bound to human leukocyte antigen (HLA) class I molecules on the surface of infected cells. This specific recognition allows the killing of virus-infected cells. The T cell immune T cell response to Chikungunya virus (CHIKV), a mosquito-borne Alphavirus of the Togaviridae family responsible for severe musculoskeletal disorders, has not been fully defined; nonetheless, the importance of HLA class I-restricted immune response in this virus has been hypothesized...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29079954/an-influenza-a-virus-vaccine-based-on-an-m2e-modified-alphavirus
#5
Haritha Ramya Krishnavajhala, Jacqueline Williams, Hans Heidner
The 23-residue external domain of the influenza A virus M2 protein (M2e) has significant potential as a vaccine antigen. Here, we describe the construction and characterization of an M2e-modified Sindbis virus designated E2S1-M2e. E2S1-M2e virions contain M2e as an N-terminal extension of the E2 glycoprotein and therefore express 240 copies of the M2e peptide on their surface. The E2S1-M2e virus expressed M2e in an accessible and immunogenic form and induced M2e-specific antibodies when administered to mice...
October 27, 2017: Archives of Virology
https://www.readbyqxmd.com/read/29070887/new-reverse-genetics-and-transfection-methods-to-rescue-arboviruses-in-mosquito-cells
#6
Thérèse Atieh, Antoine Nougairède, Raphaëlle Klitting, Fabien Aubry, Anna-Bella Failloux, Xavier de Lamballerie, Stéphane Priet
Reverse genetics is a critical tool to decrypt the biological properties of arboviruses. However, whilst reverse genetics methods have been usually applied to vertebrate cells, their use in insect cells remains uncommon due to the conjunction of laborious molecular biology techniques and of specific difficulties surrounding the transfection of such cells. To leverage reverse genetics studies in both vertebrate and mosquito cells, we designed an improved DNA transfection protocol for insect cells and then demonstrated that the simple and flexible ISA (Infectious Subgenomic Amplicons) reverse-genetics method can be efficiently applied to both mammalian and mosquito cells to generate in days recombinant infectious positive-stranded RNA viruses belonging to genera Flavivirus (Japanese encephalitis, Yellow fever, West Nile and Zika viruses) and Alphavirus (Chikungunya virus)...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29067635/interferon-regulated-gene-irg-expression-signature-in-a-mouse-model-of-chikungunya-virus-neurovirulence
#7
Sreeja R Nair, Rachy Abraham, Sankar Sundaram, Easwaran Sreekumar
Interferon regulated genes (IRGs) are critical in controlling virus infections. Here, we analyzed the expression profile of IRGs in the brain tissue in a mouse model of chikungunya virus (CHIKV) neurovirulence. Neurovirulence is one of the newer complications identified in disease caused by re-emerging strains of CHIKV, an alphavirus with positive-strand RNA in the Togaviridae family. In microarray analysis, we identified significant upregulation of 269 genes, out of which a predominant percentage (76%) was IRGs...
October 24, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29064091/dna-vaccines-for-fish-review-and-perspectives-on-correlates-of-protection
#8
REVIEW
R A Dalmo
Recently in 2016, the European Medicines Agency (EMA) recommended granting a marketing authorization in the EU for "Clynav," a DNA vaccine against salmon pancreas disease (salmonid alphavirus-3). Generally, DNA vaccines induce both early and late immune responses in fish that may be protective against disease. Several transcriptomic approaches have been performed to map immunome profiles following DNA vaccination, but the precise immune mechanism(s) that is responsible for protection is not known, although reasonable suggestions have been made...
October 24, 2017: Journal of Fish Diseases
https://www.readbyqxmd.com/read/29053568/mutation-of-a-conserved-nuclear-export-sequence-in-chikungunya-virus-capsid-protein-disrupts-host-cell-nuclear-import
#9
Susan C Jacobs, Adam Taylor, Lara J Herrero, Suresh Mahalingam, John K Fazakerley
Transmitted by mosquitoes; chikungunya virus (CHIKV) is responsible for frequent outbreaks of arthritic disease in humans. CHIKV is an arthritogenic alphavirus of the Togaviridae family. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleus. In encephalitic alphaviruses nuclear translocation induces host cell shut off; however, the role of capsid protein nuclear localisation in arthritogenic alphaviruses remains unclear. Using replicon systems, we investigated a nuclear export sequence (NES) in the N-terminal region of capsid protein; analogous to that found in encephalitic alphavirus capsid but uncharacterised in CHIKV...
October 20, 2017: Viruses
https://www.readbyqxmd.com/read/29040304/characterization-of-the-zika-virus-induced-small-rna-response-in-aedes-aegypti-cells
#10
Margus Varjak, Claire L Donald, Timothy J Mottram, Vattipally B Sreenu, Andres Merits, Kevin Maringer, Esther Schnettler, Alain Kohl
RNA interference (RNAi) controls arbovirus infections in mosquitoes. Two different RNAi pathways are involved in antiviral responses: the PIWI-interacting RNA (piRNA) and exogenous short interfering RNA (exo-siRNA) pathways, which are characterized by the production of virus-derived small RNAs of 25-29 and 21 nucleotides, respectively. The exo-siRNA pathway is considered to be the key mosquito antiviral response mechanism. In Aedes aegypti-derived cells, Zika virus (ZIKV)-specific siRNAs were produced and loaded into the exo-siRNA pathway effector protein Argonaute 2 (Ago2); although the knockdown of Ago2 did not enhance virus replication...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29040262/serological-and-spatial-analysis-of-alphavirus-and-flavivirus-prevalence-and-risk-factors-in-a-rural-community-in-western-kenya
#11
Elysse N Grossi-Soyster, Elizabeth A J Cook, William A de Glanville, Lian F Thomas, Amy R Krystosik, Justin Lee, C Njeri Wamae, Samuel Kariuki, Eric M Fèvre, A Desiree LaBeaud
Alphaviruses, such as chikungunya virus, and flaviviruses, such as dengue virus, are (re)-emerging arboviruses that are endemic in tropical environments. In Africa, arbovirus infections are often undiagnosed and unreported, with febrile illnesses often assumed to be malaria. This cross-sectional study aimed to characterize the seroprevalence of alphaviruses and flaviviruses among children (ages 5-14, n = 250) and adults (ages 15 ≥ 75, n = 250) in western Kenya. Risk factors for seropositivity were explored using Lasso regression...
October 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29031286/surveillance-of-vector-borne-infections-chikungunya-dengue-and-malaria-in-bo-sierra-leone-2012-2013
#12
Donald F Dariano, Chris R Taitt, Kathryn H Jacobsen, Umaru Bangura, Alfred S Bockarie, Moses J Bockarie, Joseph Lahai, Joseph M Lamin, Tomasz A Leski, Chadwick Yasuda, David A Stenger, Rashid Ansumana
Malaria remains a significant cause of morbidity and mortality in West Africa, but the contribution of other vector-borne infections (VBIs) to the burden of disease has been understudied. We used rapid diagnostic tests (RDTs) for three VBIs to test blood samples from 1,795 febrile residents of Bo City, Sierra Leone, over a 1-year period in 2012-2013. In total, 24% of the tests were positive for malaria, fewer than 5% were positive for markers of dengue virus infection, and 39% were positive for IgM directed against chikungunya virus (CHIKV) or a related alphavirus...
October 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29016323/enzootic-circulation-of-chikungunya-virus-in-east-africa-serological-evidence-in-nonhuman-kenyan-primates
#13
Gillian Eastwood, Rosemary C Sang, Matilde Guerbois, Evans L N Taracha, Scott C Weaver
Chikungunya virus (CHIKV) is a globally emerging pathogen causing debilitating arthralgia and fever in humans. First identified in Tanzania (1953), this mosquito-borne alphavirus received little further attention until a 2004 re-emergence in Kenya from an unknown source. This outbreak subsequently spread to the Indian Ocean, with adaptation for transmission by a new urban vector. Under the hypothesis that sylvatic progenitor cycles of CHIKV exist in Kenya (as reported in West Africa, between nonhuman primates (NHPs) and arboreal Aedes spp...
September 11, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28991178/polyprotein-processing-as-a-determinant-for-in-vitro-activity-of-semliki-forest-virus-replicase
#14
Maija K Pietilä, Irina C Albulescu, Martijn J van Hemert, Tero Ahola
Semliki Forest virus (SFV) is an arthropod-borne alphavirus that induces membrane invaginations (spherules) in host cells. These harbor the viral replication complexes (RC) that synthesize viral RNA. Alphaviruses have four replicase or nonstructural proteins (nsPs), nsP1-4, expressed as polyprotein P1234. An early RC, which synthesizes minus-strand RNA, is formed by the polyprotein P123 and the polymerase nsP4. Further proteolytic cleavage results in a late RC consisting of nsP1-4 and synthesizing plus strands...
October 7, 2017: Viruses
https://www.readbyqxmd.com/read/28981632/a-compendium-of-small-molecule-direct-acting-and-host-targeting-inhibitors-as-therapies-against-alphaviruses
#15
Kuan-Chieh Ching, Lisa F P Ng, Christina L L Chai
Alphaviruses were amongst the first arboviruses to be isolated, characterized and assigned a taxonomic status. They are globally widespread, infecting a large variety of terrestrial animals, birds, insects and even fish. Moreover, they are capable of surviving and circulating in both sylvatic and urban environments, causing considerable human morbidity and mortality. The re-emergence of Chikungunya virus (CHIKV) in almost every part of the world has caused alarm to many health agencies throughout the world...
November 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28975896/length-of-encapsidated-cargo-impacts-stability-and-structure-of-in-vitro-assembled-alphavirus-core-like-particles
#16
Vamseedhar Rayaprolu, Alan Moore, Joseph Che-Yen Wang, Boon Chong Goh, Juan Perilla, Adam Zlotnick, Suchetana Mukhopadhyay
In vitro assembly of alphavirus nucleocapsid cores, called core-like particles (CLPs), require a polyanionic cargo. There are no sequence or structure requirements to encapsidate single-stranded nucleic acid cargo. In this work, we wanted to determine how the length of the cargo impacts the stability and structure of the assembled CLPs. We hypothesized that cargo neutralizes the basic region of the alphavirus capsid protein and, if the cargo is long enough, will also act to scaffold the CP monomers together...
October 4, 2017: Journal of Physics. Condensed Matter: An Institute of Physics Journal
https://www.readbyqxmd.com/read/28975709/ubiquitin-conjugating-enzyme-e2-l3-is-downregulated-by-the-chikungunya-virus-nsp2-protease
#17
Suwipa Ramphan, Sarawut Khongwichit, Chonticha Saisawang, Duangnapa Kovanich, Albert J Ketterman, Sukathida Ubol, Prasert Auewarakul, Sittiruk Roytrakul, Duncan R Smith, Atichat Kuadkitkan
PURPOSE: Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus that causes chikungunya fever in humans. The CHIKV nonstructural protein 2 (nsP2) is a multifunctional protein that additionally modulates the host cell to dampen the innate immune response and inhibit other cellular processes. EXPERIMENTAL DESIGN: To further investigate the interactions of nsP2 with host cells, the protease domain of CHIKV nsP2 (nsP2-pro) was transfected into Hela cells, and differential protein expression was detected by 2-dimension (2D) polyacrylamide gel electrophoresis...
October 4, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28961161/venezuelan-equine-encephalitis-virus-capsid-the-clever-caper
#18
REVIEW
Lindsay Lundberg, Brian Carey, Kylene Kehn-Hall
Venezuelan equine encephalitis virus (VEEV) is a New World alphavirus that is vectored by mosquitos and cycled in rodents. It can cause disease in equines and humans characterized by a febrile illness that may progress into encephalitis. Like the capsid protein of other viruses, VEEV capsid is an abundant structural protein that binds to the viral RNA and interacts with the membrane-bound glycoproteins. It also has protease activity, allowing cleavage of itself from the growing structural polypeptide during translation...
September 29, 2017: Viruses
https://www.readbyqxmd.com/read/28956592/fusion-of-a-new-world-alphavirus-with-membrane-microdomains-involving-partially-reversible-conformational-changes-in-the-viral-spike-proteins
#19
Ivanildo P Sousa, Carlos A M Carvalho, Ygara S Mendes, Gilberto Weissmuller, Andréa C Oliveira, Andre M O Gomes
Alphaviruses are enveloped arboviruses mainly proposed to infect host cells by receptor-mediated endocytosis followed by fusion between the viral envelope and the endosomal membrane. The fusion reaction is triggered by low pH and requires the presence of both cholesterol and sphingolipids in the target membrane, suggesting the involvement of lipid rafts in the cell entry mechanism. In this study, we show for the first time the interaction of an enveloped virus with membrane microdomains isolated from living cells...
October 31, 2017: Biochemistry
https://www.readbyqxmd.com/read/28955951/cadmium-reduces-the-efficiency-of-sindbis-virus-replication-in-human-cells-and-promotes-their-survival-by-inhibiting-apoptosis
#20
Etienne Frumence, Marjolaine Roche, Pascale Guiraud
Arthritogenic alphaviruses are emerging arthropod-borne viruses that occasionally cause sporadic to global outbreaks all over the world. Many environmental factors including xenobiotics have been identified as capable of influencing the spread, the susceptibility and the outcome of viral infection. Among them cadmium is a toxic non-essential heavy metal and a prevalent environmental contaminant. In the present study we evaluated the effect of cadmium exposure on alphavirus infection in vitro. We infected Human Embryonic Kidney (HEK) 293 cells in the presence of cadmium chloride (CdCl2) with Sindbis virus...
December 2016: Biochemistry and Biophysics Reports
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