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https://www.readbyqxmd.com/read/29321331/germline-igm-is-sufficient-but-not-required-for-antibody-mediated-alphavirus-clearance-from-the-central-nervous-system
#1
Voraphoj Nilaratanakul, Jie Chen, Oanh Tran, Victoria K Baxter, Elizabeth M Troisi, Jane X Yeh, Diane E Griffin
Sindbis virus (SINV) infection of neurons in the brain and spinal cord in mice provides a model system for investigating recovery from encephalomyelitis and antibody-mediated clearance of virus from the central nervous system (CNS). To determine the roles of IgM and IgG in recovery, we compared the responses of immunoglobulin-deficient activation-induced adenosine deaminase (AID)-/-, secretory IgM (sIgM)-/- and AID-/- sIgM-/- double knock out (DKO) mice with wild-type (WT) C57BL/6 mice for disease, clearance of infectious virus and viral RNA from brain and spinal cord, antibody responses and B cell infiltration into the CNS...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29321325/the-identification-and-characterization-of-sindbis-virus-rna-host-protein-interactions
#2
Autumn T LaPointe, Natasha N Gebhart, Megan E Meller, Richard W Hardy, Kevin J Sokoloski
Arthropod-borne viruses, such as the members of genus Alphavirus, are a significant concern to global public health. As obligate intracellular pathogens, RNA viruses must interact with the host cell machinery to establish, and complete, their viral lifecycles. Despite considerable efforts to define the host/pathogen interactions essential for alphaviral replication, an unbiased and inclusive assessment of alphaviral RNA:protein interactions has not been undertaken. Moreover, the biological and molecular importance of these interactions, in the full context of their molecular function as RNA-binding proteins, has not been fully realized...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29306785/structure-function-insights-into-chikungunya-virus-capsid-protein-small-molecules-targeting-capsid-hydrophobic-pocket
#3
Rajesh Sharma, Pooja Kesari, Pravindra Kumar, Shailly Tomar
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. Molecular contacts between CP-cdE2 were determined by fitting structures of CHIKV CP and cdE2 into the cryo-EM map of Venezuelan equine encephalitis virus (VEEV). Binding of (S)-(+)-Mandelic acid (MDA) and Ethyl 3-aminobenzoate (EAB) to the hydrophobic pocket of CP was evaluated by molecular docking...
January 4, 2018: Virology
https://www.readbyqxmd.com/read/29300359/geometric-defects-and-icosahedral-viruses
#4
REVIEW
Joseph Che-Yen Wang, Suchetana Mukhopadhyay, Adam Zlotnick
We propose that viruses with geometric defects are not necessarily flawed viruses. A geometric defect may be a reactive site. Defects may facilitate assembly, dissociation, or accessibility of cellular proteins to virion components. In single molecule studies of hepadnavirus assembly, defects and overgrowth are common features. Icosahedral alphaviruses and flaviviruses, among others, have capsids with geometric defects. Similarly, immature retroviruses, which are non-icosahedral, have numerous "errors". In many viruses, asymmetric exposure of interior features allows for regulated genome release or supports intracellular trafficking...
January 4, 2018: Viruses
https://www.readbyqxmd.com/read/29287681/alphavirus-vector-based-replicon-particles-expressing-multivalent-cross-protective-lassa-virus-glycoproteins
#5
Min Wang, Jenny Jokinen, Irina Tretyakova, Peter Pushko, Igor S Lukashevich
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. We developed multivalent virus-like particle vectors (VLPVs) derived from the human Venezuelan equine encephalitis TC-83 IND vaccine (VEEV) as the next generation of alphavirus-based bicistronic RNA replicon particles. The genes encoding VEEV structural proteins were replaced with LASV glycoproteins (GPC) from distantly related clades I and IV with individual 26S promoters...
December 26, 2017: Vaccine
https://www.readbyqxmd.com/read/29287308/chikungunya-virus-arthritis-implications-of-acute-and-chronic-inflammation-mechanisms-on-patient-management
#6
REVIEW
Ali Zaid, Patrick Gérardin, Adam Taylor, Helen Mostafavi, Denis Malvy, Suresh Mahalingam
In the past decade, arboviruses - arthropod-borne viruses - have been the focus of public health institutions worldwide following a spate of devastating outbreaks. Chikungunya virus (CHIKV), an arbovirus that belongs to the alphavirus genus, is a re-emerging arthritogenic virus that has caused explosive outbreaks since 2006, notably in the Reunion Island, and more recently in the Caribbean, South America, India and South-East Asia. The severity of arthritic disease caused by CHIKV has prompted public health authorities of affected countries to develop specific guidelines to tackle this pathogen...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29285673/detection-isolation-and-characterization-of-chikungunya-viruses-associated-with-the-pakistan-outbreak-of-2016-2017
#7
Si-Qing Liu, Xiao Li, Ya-Nan Zhang, Ai-Li Gao, Cheng-Lin Deng, Jun-Hua Li, Shoukat Jehan, Nadia Jamil, Fei Deng, Hongping Wei, Bo Zhang
The chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus, which has infected millions of people in Africa, Asia, Americas, and Europe since it reemerged in India and Indian Ocean regions in 2005-2006. Starting in the middle of November 2016, CHIKV has been widely spread, and more than 4,000 cases of infections in humans were confirmed in Pakistan. Here, we report the first isolation and characterization of CHIKV from the Pakistan outbreak. Eight CHIKV strains were newly isolated from human serum samples using a cell culture procedure...
December 21, 2017: Virologica Sinica
https://www.readbyqxmd.com/read/29281739/lower-temperatures-reduce-type-i-interferon-activity-and-promote-alphaviral-arthritis
#8
Natalie A Prow, Bing Tang, Joy Gardner, Thuy T Le, Adam Taylor, Yee S Poo, Eri Nakayama, Thiago D C Hirata, Helder I Nakaya, Andrii Slonchak, Pamela Mukhopadhyay, Suresh Mahalingam, Wayne A Schroder, William Klimstra, Andreas Suhrbier
Chikungunya virus (CHIKV) belongs to a group of mosquito-borne alphaviruses associated with acute and chronic arthropathy, with peripheral and limb joints most commonly affected. Using a mouse model of CHIKV infection and arthritic disease, we show that CHIKV replication and the ensuing foot arthropathy were dramatically reduced when mice were housed at 30°C, rather than the conventional 22°C. The effect was not associated with a detectable fever, but was dependent on type I interferon responses. Bioinformatics analyses of RNA-Seq data after injection of poly(I:C)/jetPEI suggested the unfolded protein response and certain type I interferon responses are promoted when feet are slightly warmer...
December 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29244871/inflammatory-monocytes-mediate-control-of-acute-alphavirus-infection-in-mice
#9
Kelsey C Haist, Kristina S Burrack, Bennett J Davenport, Thomas E Morrison
Chikungunya virus (CHIKV) and Ross River virus (RRV) are mosquito-transmitted alphaviruses that cause debilitating acute and chronic musculoskeletal disease. Monocytes are implicated in the pathogenesis of these infections; however, their specific roles are not well defined. To investigate the role of inflammatory Ly6ChiCCR2+ monocytes in alphavirus pathogenesis, we used CCR2-DTR transgenic mice, enabling depletion of these cells by administration of diptheria toxin (DT). DT-treated CCR2-DTR mice displayed more severe disease following CHIKV and RRV infection and had fewer Ly6Chi monocytes and NK cells in circulation and muscle tissue compared with DT-treated WT mice...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29224194/establishment-and-evaluation-of-an-indirect-immunofluorescence-assay-for-the-detection-of-salmonid-alphavirus
#10
S Gao, W Shi, Y T Wang, M T Guo, K X Duan, A C Song, G H Lian, Tong Ren, Y J Li, L J Tang, L Sun, M Liu
Salmonid alphaviruses (SAV) severely infects farmed salmonids and rainbow trout. Owing to the recent increase in fish import trade, several SAV-unreported countries, such as China, may face serious threat of this infection. Thus, it is necessary to develop efficient detection methods for the prevention and diagnosis of SAV infection. In this study, we selected a conserved segment of the SAV E1 protein as a target immunogen for the preparation of monoclonal antibodies (mAbs) specific to SAV. A sensitive indirect immunofluorescence (IF) method was developed using 26E9C2 mAb that detected E1 protein and identified subtypes 1, 2 and 5 of SAV...
December 9, 2017: Letters in Applied Microbiology
https://www.readbyqxmd.com/read/29216317/novel-wolbachia-transinfected-aedes-aegypti-mosquitoes-possess-diverse-fitness-and-vector-competence-phenotypes
#11
Johanna E Fraser, Jyotika Taneja De Bruyne, Iñaki Iturbe-Ormaetxe, Justin Stepnell, Rhiannon L Burns, Heather A Flores, Scott L O'Neill
Wolbachia pipientis from Drosophila melanogaster (wMel) is an endosymbiotic bacterium that restricts transmission of human pathogenic flaviviruses and alphaviruses, including dengue, Zika, and chikungunya viruses, when introduced into the mosquito vector Aedes aegypti. To date, wMel-infected Ae. aegypti have been released in field trials in 5 countries to evaluate the effectiveness of this strategy for disease control. Despite the success in establishing wMel-infected mosquitoes in wild populations, and the well-characterized antiviral capabilities of wMel, transinfecting different or additional Wolbachia strains into Ae...
December 7, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29203665/structural-studies-of-chikungunya-virus-maturation
#12
Moh Lan Yap, Thomas Klose, Akane Urakami, S Saif Hasan, Wataru Akahata, Michael G Rossmann
Cleavage of the alphavirus precursor glycoprotein p62 into the E2 and E3 glycoproteins before assembly with the nucleocapsid is the key to producing fusion-competent mature spikes on alphaviruses. Here we present a cryo-EM, 6.8-Å resolution structure of an "immature" Chikungunya virus in which the cleavage site has been mutated to inhibit proteolysis. The spikes in the immature virus have a larger radius and are less compact than in the mature virus. Furthermore, domains B on the E2 glycoproteins have less freedom of movement in the immature virus, keeping the fusion loops protected under domain B...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29194359/chikungunya-virus-pathophysiology-mechanism-and-modeling
#13
REVIEW
Vaishnavi K Ganesan, Bin Duan, St Patrick Reid
Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, is recurring in epidemic waves. In the past decade and a half, the disease has resurged in several countries around the globe, with outbreaks becoming increasingly severe. Though CHIKV was first isolated in 1952, there remain significant gaps in knowledge of CHIKV biology, pathogenesis, transmission, and mechanism. Diagnosis is largely simplified and based on symptoms, while treatment is supportive rather than curative. Here we present an overview of the disease, the challenges that lie ahead for future research, and what directions current studies are headed towards, with emphasis on improvement of current animal models and potential use of 3D models...
December 1, 2017: Viruses
https://www.readbyqxmd.com/read/29187545/novel-insect-specific-eilat-virus-based-chimeric-vaccine-candidates-provide-durable-mono-and-multi-valent-single-dose-protection-against-lethal-alphavirus-challenge
#14
Jesse H Erasmus, Robert L Seymour, Jason T Kaelber, Dal Y Kim, Grace Leal, Michael B Sherman, Ilya Frolov, Wah Chiu, Scott C Weaver, Farooq Nasar
Most alphaviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates including birds, rodents, equids, humans and nonhuman primates. Recently, a host-restricted, mosquito-borne alphavirus, Eilat virus (EILV), was described with an inability to infect vertebrate cells based on defective attachment and/or entry as well as a lack of genomic RNA replication. We investigated the utilization of EILV recombinant technology as a vaccine platform against eastern (EEEV) and Venezuelan equine encephalitis viruses (VEEV), two important pathogens of humans and domesticated animals...
November 29, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29185115/the-synergistic-effect-of-nsp2-l618-nsp3-r117-and-e2-k187-on-the-large-plaque-phenotype-of-chikungunya-virus
#15
Benjawan Thoka, Thitigun Jaimipak, Supachoke Onnome, Sutee Yoksan, Sukathida Ubol, Rojjanaporn Pulmanausahakul
Chikungunya virus (CHIKV), a mosquito-borne Alphavirus, is the etiological agent of chikungunya fever. CHIKV re-emerged from 2004 onwards, and subsequently caused major outbreaks in many parts of the world including the Indian Ocean islands, Asia, and the Americas. In this study, a large plaque variant of CHIKV isolated from patient in Thailand was subjected to repeated cycles of plaque-purification in Vero cells. The resulting virus produced homogenous large plaques and showed a more pathogenic phenotype than the parental wild-type CHIKV...
November 28, 2017: Virus Genes
https://www.readbyqxmd.com/read/29182144/chikungunya-virus-disease-among-travelers-united-states-2014-2016
#16
Nicole P Lindsey, J Erin Staples, Marc Fischer
Chikungunya virus is a mosquito-borne alphavirus that causes an acute febrile illness with severe polyarthralgia. The first local transmission of chikungunya virus in the Western Hemisphere was reported in December 2013. In the following year, the virus spread throughout much of the Americas and the number of cases among travelers increased substantially. We reviewed the epidemiology of chikungunya virus disease cases reported among U.S. travelers from 2014 to 2016. A total of 3,941 travel-acquired cases were reported from 49 states and the District of Columbia; 3,616 (92%) reported travel to other countries or territories in the Americas; the remaining 8% reported travel to Asia, Africa, or the Western Pacific...
November 27, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29175515/innate-immune-control-of-alphavirus-infection
#17
REVIEW
Kathryn S Carpentier, Thomas E Morrison
Alphaviruses are important human pathogens that cause diseases ranging from acute and chronic polyarthralgia to encephalitis. Transmitted by mosquito vectors, alphaviruses have high potential for emergence and have initiated several recent epidemics. The innate immune response is critical for controlling the acute phase of alphavirus disease, and the induction of type I interferon (IFN) is essential in this response. In this review, we discuss our current understanding of innate host sensors that initiate antiviral responses following alphavirus infection, and the IFN-induced effector proteins that limit alphavirus replication and dissemination...
November 22, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/29169832/a-novel-insect-infecting-virga-nege-like-virus-group-and-its-pervasive-endogenization-into-insect-genomes
#18
Hideki Kondo, Sotaro Chiba, Kazuyuki Maruyama, Ida Bagus Andika, Nobuhiro Suzuki
Insects are the host and vector of diverse viruses including those that infect vertebrates, plants, and fungi. Recent wide-scale transcriptomic analyses have uncovered the existence of a number of novel insect viruses belonging to an alphavirus-like superfamily (virgavirus/negevirus-related lineage). In this study, through an in silico search using publicly available insect transcriptomic data, we found numerous virus-like sequences related to insect virga/nege-like viruses. Phylogenetic analysis showed that these novel viruses and related virus-like sequences fill the major phylogenetic gaps between insect and plant virga/negevirus lineages...
November 20, 2017: Virus Research
https://www.readbyqxmd.com/read/29167335/%C3%AE-d-n-4-hydroxycytidine-is-a-potent-anti-alphavirus-compound-that-induces-high-level-of-mutations-in-viral-genome
#19
Nadya Urakova, Valeriya Kuznetsova, David K Crossman, Arpine Sokratian, David B Guthrie, Alexander A Kolykhalov, Mark A Lockwood, Michael G Natchus, Michael R Crowley, George R Painter, Elena I Frolova, Ilya Frolov
Venezuelan equine encephalitis virus (VEEV) is a representative member of the New World alphaviruses. It is transmitted by mosquito vectors and causes highly debilitating disease in humans, equides and other vertebrate hosts. Despite a continuous public health threat, very few compounds with anti-VEEV activity in cell culture and in mouse models have been identified to date, and rapid development of virus resistance to some of them has been recorded. In this study, we investigated the possibility of using a modified nucleoside analog, β-D-N(4)-hydroxycytidine (NHC), as an anti-VEEV agent and defined the mechanism of its anti-VEEV activity...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29161110/biotechnological-applications-of-an-insect-specific-alphavirus
#20
Jesse H Erasmus, Scott C Weaver
The coupling of viral and arthropod host diversity, with evolving methods of virus discovery, has resulted in the identification and classification of a growing number of novel insect-specific viruses (ISVs) that appear to be evolutionarily related to many human pathogens but have either lost or have yet to gain the ability to replicate in vertebrates. The discovery of ISVs has raised many questions as to the origin and evolution of many human pathogenic viruses and points to the role that arthropods may play in this evolutionary process...
November 21, 2017: DNA and Cell Biology
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