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Journal articles on the topic 'Alphavirus'

Author: Grafiati

Published: 4 June 2021

Last updated: 25 July 2025

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1

Mostafavi, Helen, Eranga Abeyratne, Ali Zaid, and Adam Taylor. "Arthritogenic Alphavirus-Induced Immunopathology and Targeting Host Inflammation as A Therapeutic Strategy for Alphaviral Disease." Viruses 11, no. 3 (2019): 290. http://dx.doi.org/10.3390/v11030290.

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Arthritogenic alphaviruses are a group of medically important arboviruses that cause inflammatory musculoskeletal disease in humans with debilitating symptoms, such as arthralgia, arthritis, and myalgia. The arthritogenic, or Old World, alphaviruses are capable of causing explosive outbreaks, with some viruses of major global concern. At present, there are no specific therapeutics or commercially available vaccines available to prevent alphaviral disease. Infected patients are typically treated with analgesics and non-steroidal anti-inflammatory drugs to provide often inadequate symptomatic re

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2

Landers, V. Douglas, Daniel W. Wilkey, Michael L. Merchant, Thomas C. Mitchell, and Kevin J. Sokoloski. "The Alphaviral Capsid Protein Inhibits IRAK1-Dependent TLR Signaling." Viruses 13, no. 3 (2021): 377. http://dx.doi.org/10.3390/v13030377.

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Alphaviruses are arthropod-borne RNA viruses which can cause either mild to severe febrile arthritis which may persist for months, or encephalitis which can lead to death or lifelong cognitive impairments. The non-assembly molecular role(s), functions, and protein–protein interactions of the alphavirus capsid proteins have been largely overlooked. Here we detail the use of a BioID2 biotin ligase system to identify the protein–protein interactions of the Sindbis virus capsid protein. These efforts led to the discovery of a series of novel host–pathogen interactions, including the identification

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3

Kaelber, Jason T., David Chmielewski, Wah Chiu, and Albert J. Auguste. "Alphavirus Particles Can Assemble with an Alternate Triangulation Number." Viruses 14, no. 12 (2022): 2650. http://dx.doi.org/10.3390/v14122650.

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Alphaviruses are spherical, enveloped RNA viruses primarily transmitted by mosquitoes, and cause significant arthritogenic and neurotropic disease in humans and livestock. Previous reports have shown that—in contrast to prototypical icosahedral viruses—alphaviruses incorporate frequent defects, and these may serve important functions in the viral life cycle. We confirm the genus-wide pleomorphism in live viral particles and extend our understanding of alphavirus assembly through the discovery of an alternate architecture of Eastern equine encephalitis virus (EEEV) particles. The alternate T =

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4

Bedoui, Yosra, Dauriane De Larichaudy, Matthieu Daniel, et al. "Deciphering the Role of Schwann Cells in Inflammatory Peripheral Neuropathies Post Alphavirus Infection." Cells 12, no. 1 (2022): 100. http://dx.doi.org/10.3390/cells12010100.

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Old world alphaviruses (e.g., chikungunya) are known to cause severe acute and chronic debilitating arthralgia/arthritis. However, atypical neurological manifestations and, in particular, unexpected cases of acute inflammatory Guillain–Barre syndrome (GBS) have been associated with the arthritogenic alphaviruses. The pathogenesis of alphavirus-associated GBS remains unclear. We herein addressed for the first time the role of Schwann cells (SC) in peripheral neuropathy post-alphaviral infection using the prototypical ONNV alphavirus model. We demonstrated that human SC expressed the recently id

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5

Cherkashchenko, Liubov, Kai Rausalu, Sanjay Basu, Luke Alphey, and Andres Merits. "Expression of Alphavirus Nonstructural Protein 2 (nsP2) in Mosquito Cells Inhibits Viral RNA Replication in Both a Protease Activity-Dependent and -Independent Manner." Viruses 14, no. 6 (2022): 1327. http://dx.doi.org/10.3390/v14061327.

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Alphaviruses are positive-strand RNA viruses, mostly being mosquito-transmitted. Cells infected by an alphavirus become resistant to superinfection due to a block that occurs at the level of RNA replication. Alphavirus replication proteins, called nsP1-4, are produced from nonstructural polyprotein precursors, processed by the protease activity of nsP2. Trans-replicase systems and replicon vectors were used to study effects of nsP2 of chikungunya virus and Sindbis virus on alphavirus RNA replication in mosquito cells. Co-expressed wild-type nsP2 reduced RNA replicase activity of homologous vir

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6

Souza-Souza, Kauê F. C., Cassiano F. Gonçalves-de-Albuquerque, Cláudio Cirne-Santos, Izabel C. N. P. Paixão, and Patrícia Burth. "Alphavirus Replication: The Role of Cardiac Glycosides and Ion Concentration in Host Cells." BioMed Research International 2020 (May 9, 2020): 1–7. http://dx.doi.org/10.1155/2020/2813253.

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Alphaviruses are arthropod-borne viruses that can cause fever, rash, arthralgias, and encephalitis. The mosquito species Aedes aegypti and Aedes albopictus are the most frequent transmitters of alphaviruses. There are no effective vaccines or specific antivirals available for the treatment of alphavirus-related infections. Interestingly, changes in ion concentration in host cells have been characterized as critical regulators of the alphavirus life cycle, including fusion with the host cell, glycoprotein trafficking, genome translation, and viral budding. Cardiac glycosides, which are classica

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7

Powers, Ann M., Aaron C. Brault, Yukio Shirako, et al. "Evolutionary Relationships and Systematics of the Alphaviruses." Journal of Virology 75, no. 21 (2001): 10118–31. http://dx.doi.org/10.1128/jvi.75.21.10118-10131.2001.

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ABSTRACT Partial E1 envelope glycoprotein gene sequences and complete structural polyprotein sequences were used to compare divergence and construct phylogenetic trees for the genus Alphavirus. Tree topologies indicated that the mosquito-borne alphaviruses could have arisen in either the Old or the New World, with at least two transoceanic introductions to account for their current distribution. The time frame for alphavirus diversification could not be estimated because maximum-likelihood analyses indicated that the nucleotide substitution rate varies considerably across sites within the geno

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8

Lundstrom, Kenneth. "Alphaviruses in Immunotherapy and Anticancer Therapy." Biomedicines 10, no. 9 (2022): 2263. http://dx.doi.org/10.3390/biomedicines10092263.

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Alphaviruses have been engineered as expression vectors for vaccine development and gene therapy. Due to the feature of RNA self-replication, alphaviruses can provide exceptional direct cytoplasmic expression of transgenes based on the delivery of recombinant particles, naked or nanoparticle-encapsulated RNA or plasmid-based DNA replicons. Alphavirus vectors have been utilized for the expression of various antigens targeting different types of cancers, and cytotoxic and antitumor genes. The most common alphavirus vectors are based on the Semliki Forest virus, Sindbis virus and Venezuelan equin

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9

Rao, Shambhavi, and Adam Taylor. "Arthritogenic Alphavirus Capsid Protein." Life 11, no. 3 (2021): 230. http://dx.doi.org/10.3390/life11030230.

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In the past two decades Old World and arthritogenic alphavirus have been responsible for epidemics of polyarthritis, causing high morbidity and becoming a major public health concern. The multifunctional arthritogenic alphavirus capsid protein is crucial for viral infection. Capsid protein has roles in genome encapsulation, budding and virion assembly. Its role in multiple infection processes makes capsid protein an attractive target to exploit in combating alphaviral infection. In this review, we summarize the function of arthritogenic alphavirus capsid protein, and describe studies that have

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10

Xie, Yifan, Jie Cao, Shuyi Gan, et al. "TRIM32 inhibits Venezuelan equine encephalitis virus infection by targeting a late step in viral entry." PLOS Pathogens 20, no. 11 (2024): e1012312. http://dx.doi.org/10.1371/journal.ppat.1012312.

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Alphaviruses are mosquito borne RNA viruses that are a reemerging public health threat. Alphaviruses have a broad host range, and can cause diverse disease outcomes like arthritis, and encephalitis. The host ubiquitin proteasome system (UPS) plays critical roles in regulating cellular processes to control the infections with various viruses, including alphaviruses. Previous studies suggest alphaviruses hijack UPS for virus infection, but the molecular mechanisms remain poorly characterized. In addition, whether certain E3 ubiquitin ligases or deubiquitinases act as alphavirus restriction facto

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11

Nguyen, LeAnn P., Kelly S. Aldana, Emily Yang, Zhenlan Yao, and Melody M. H. Li. "Alphavirus Evasion of Zinc Finger Antiviral Protein (ZAP) Correlates with CpG Suppression in a Specific Viral nsP2 Gene Sequence." Viruses 15, no. 4 (2023): 830. http://dx.doi.org/10.3390/v15040830.

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Certain re-emerging alphaviruses, such as chikungunya virus (CHIKV), cause serious disease and widespread epidemics. To develop virus-specific therapies, it is critical to understand the determinants of alphavirus pathogenesis and virulence. One major determinant is viral evasion of the host interferon response, which upregulates antiviral effectors, including zinc finger antiviral protein (ZAP). Here, we demonstrated that Old World alphaviruses show differential sensitivity to endogenous ZAP in 293T cells: Ross River virus (RRV) and Sindbis virus (SINV) are more sensitive to ZAP than o’nyong’

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12

Lundstrom, Kenneth. "Self-Replicating Alphaviruses: From Pathogens to Therapeutic Agents." Viruses 16, no. 11 (2024): 1762. http://dx.doi.org/10.3390/v16111762.

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Alphaviruses are known for being model viruses for studying cellular functions related to viral infections but also for causing epidemics in different parts of the world. More recently, alphavirus-based expression systems have demonstrated efficacy as vaccines against infectious diseases and as therapeutic applications for different cancers. Point mutations in the non-structural alphaviral replicase genes have generated enhanced transgene expression and created temperature-sensitive expression vectors. The recently engineered trans-amplifying RNA system can provide higher translational efficie

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13

Henss, Lisa, Constanze Yue, Joshua Kandler, et al. "Establishment of an Alphavirus-Specific Neutralization Assay to Distinguish Infections with Different Members of the Semliki Forest complex." Viruses 11, no. 1 (2019): 82. http://dx.doi.org/10.3390/v11010082.

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Background: Alphaviruses are transmitted by arthropod vectors and can be found worldwide. Alphaviruses of the Semliki Forest complex such as chikungunya virus (CHIKV), Mayaro virus (MAYV) or Ross River virus (RRV) cause acute febrile illness and long-lasting arthralgia in humans, which cannot be clinically discriminated from a dengue virus or Zika virus infection. Alphaviruses utilize a diverse array of mosquito vectors for transmission and spread. For instance, adaptation of CHIKV to transmission by Aedes albopictus has increased its spread and resulted in large outbreaks in the Indian Ocean

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14

Stepanov, Aleksandr V., Ilya V. Yudnikov, and Aleksandr V. Kvardakov. "Alphaviruses: a modern view on the problem." Bulletin of the Russian Military Medical Academy 24, no. 1 (2022): 135–42. http://dx.doi.org/10.17816/brmma76901.

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At present, infectious diseases of alphaviral etiology remain relevant. The study examined the characteristics of alphaviruses, including the present knowledge of the structure and replication of the virion; prevalence of epidemiologically significant species and potential distribution areas of some alphaviruses; pathogenesis and clinical presentation of causative diseases, diagnosis, prevention, and treatment; and their possible use as pathogenic biological agents. Sixteen strains of alphaviruses are hazardous to human health, and some of them can disrupt human activities. Areas with alphavir

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15

Rangel, Margarita V., and Kenneth A. Stapleford. "Alphavirus Virulence Determinants." Pathogens 10, no. 8 (2021): 981. http://dx.doi.org/10.3390/pathogens10080981.

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Alphaviruses are important pathogens that continue to cause outbreaks of disease in humans and animals worldwide. Diseases caused by alphavirus infections include acute symptoms of fever, rash, and nausea as well as chronic arthritis and severe-to-fatal conditions including myocarditis and encephalitis. Despite their prevalence and the significant public health threat they pose, there are currently no effective antiviral treatments or vaccines against alphaviruses. Various genetic determinants of alphavirus virulence, including genomic RNA elements and specific protein residues and domains, ha

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16

Lundstrom, Kenneth. "Plasmid DNA-based Alphavirus Vaccines." Vaccines 7, no. 1 (2019): 29. http://dx.doi.org/10.3390/vaccines7010029.

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Alphaviruses have been engineered as vectors for high-level transgene expression. Originally, alphavirus-based vectors were applied as recombinant replication-deficient particles, subjected to expression studies in mammalian and non-mammalian cell lines, primary cell cultures, and in vivo. However, vector engineering has expanded the application range to plasmid DNA-based delivery and expression. Immunization studies with DNA-based alphavirus vectors have demonstrated tumor regression and protection against challenges with infectious agents and tumor cells in animal tumor models. The presence

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17

Malonis, Ryan J., James T. Earnest, Arthur S. Kim, et al. "Near-germline human monoclonal antibodies neutralize and protect against multiple arthritogenic alphaviruses." Proceedings of the National Academy of Sciences 118, no. 37 (2021): e2100104118. http://dx.doi.org/10.1073/pnas.2100104118.

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Arthritogenic alphaviruses are globally distributed, mosquito-transmitted viruses that cause rheumatological disease in humans and include Chikungunya virus (CHIKV), Mayaro virus (MAYV), and others. Although serological evidence suggests that some antibody-mediated heterologous immunity may be afforded by alphavirus infection, the extent to which broadly neutralizing antibodies that protect against multiple arthritogenic alphaviruses are elicited during natural infection remains unknown. Here, we describe the isolation and characterization of MAYV-reactive alphavirus monoclonal antibodies (mAb

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18

La Linn, May, Joy Gardner, David Warrilow, et al. "Arbovirus of Marine Mammals: a New Alphavirus Isolated from the Elephant Seal Louse, Lepidophthirus macrorhini." Journal of Virology 75, no. 9 (2001): 4103–9. http://dx.doi.org/10.1128/jvi.75.9.4103-4109.2001.

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ABSTRACT A novel alphavirus was isolated from the louse Lepidophthirus macrorhini, collected from southern elephant seals,Mirounga leonina, on Macquarie Island, Australia. The virus displayed classic alphavirus ultrastructure and appeared to be serologically different from known Australasian alphaviruses. Nearly all Macquarie Island elephant seals tested had neutralizing antibodies against the virus, but no virus-associated pathology has been identified. Antarctic Division personnel who have worked extensively with elephant seals showed no serological evidence of exposure to the virus. Sequenc

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19

Torres-Ruesta, Anthony, Rhonda Sin-Ling Chee, and Lisa F. P. Ng. "Insights into Antibody-Mediated Alphavirus Immunity and Vaccine Development Landscape." Microorganisms 9, no. 5 (2021): 899. http://dx.doi.org/10.3390/microorganisms9050899.

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Alphaviruses are mosquito-borne pathogens distributed worldwide in tropical and temperate areas causing a wide range of symptoms ranging from inflammatory arthritis-like manifestations to the induction of encephalitis in humans. Historically, large outbreaks in susceptible populations have been recorded followed by the development of protective long-lasting antibody responses suggesting a potential advantageous role for a vaccine. Although the current understanding of alphavirus antibody-mediated immunity has been mainly gathered in natural and experimental settings of chikungunya virus (CHIKV

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20

Luers, Aimée J., Sandra D. Adams, John V. Smalley, and James J. Campanella. "A Phylogenomic Study of the Genus Alphavirus Employing Whole Genome Comparison." Comparative and Functional Genomics 6, no. 4 (2005): 217–27. http://dx.doi.org/10.1002/cfg.478.

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The phylogenetics of the genus Alphavirus have historically been characterized using partial gene, single gene or partial proteomic data. We have mined cDNA and amino acid sequences from GenBank for all fully sequenced and some partially sequenced alphaviruses and generated phylogenomic analyses of the genus Alphavirus genus, employing capsid encoding structural regions, non-structural coding regions and complete viral genomes. Our studies support the presence of the previously reported recombination event that produced the Western Equine Encephalitis clade, and confirm many of the patterns of

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21

Pampeno, Christine, Alicia Hurtado, Silvana Opp, and Daniel Meruelo. "Channeling the Natural Properties of Sindbis Alphavirus for Targeted Tumor Therapy." International Journal of Molecular Sciences 24, no. 19 (2023): 14948. http://dx.doi.org/10.3390/ijms241914948.

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Sindbis alphavirus vectors offer a promising platform for cancer therapy, serving as valuable models for alphavirus-based treatment. This review emphasizes key studies that support the targeted delivery of Sindbis vectors to tumor cells, highlighting their effectiveness in expressing tumor-associated antigens and immunomodulating proteins. Among the various alphavirus vectors developed for cancer therapy, Sindbis-vector-based imaging studies have been particularly extensive. Imaging modalities that enable the in vivo localization of Sindbis vectors within lymph nodes and tumors are discussed.

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Costlow, Jessica L., Erika S. Krow, and J. Jordan Steele. "Imatinib Mesylate as an Effective Anti-viral Treatment for Alphavirus Infections." Fine Focus 3, no. 2 (2017): 141–52. http://dx.doi.org/10.33043/ff.3.2.141-152.

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Alphaviruses are plus-strand RNA viruses that are transmitted by mosquitoes. There are very limited vaccines and treatment options available to those infected with alphaviruses, resulting in significant human and animal morbidity and mortality each year. Viruses are parasites of host cell metabolism and alphaviruses have been shown to increase glycolytic flux during infection to aid viral replication. Imatinib mesylate is an FDA-approved tyrosine kinase inhibitor that is used to treat several types of cancers. A hallmark of tumorous cells is an elevated metabolic rate and Imatinib successfully

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Deperasińska, Izabela, Patrycja Schulz, and Andrzej K. Siwicki. "Salmonid alphavirus (SAV)." Journal of Veterinary Research 62, no. 1 (2018): 1–6. http://dx.doi.org/10.2478/jvetres-2018-0001.

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AbstractSalmonid alphavirus (SAV), genus Alphavirus, family Togaviridae, is a single-stranded RNA virus affecting Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). It is known to be responsible for pancreas disease (PD) and sleeping disease (SD) which are increasing problems, causing high fish mortality and economic losses in the European aquaculture industry. Pancreas disease was first described in Atlantic salmon in Scotland in 1976 and a similar disease caused by the closely related sleeping disease virus was first described in rainbow trout in France. There have also b

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Taylor, Adam, Julian V. Melton, Lara J. Herrero, et al. "Effects of an In-Frame Deletion of the6kGene Locus from the Genome of Ross River Virus." Journal of Virology 90, no. 8 (2016): 4150–59. http://dx.doi.org/10.1128/jvi.03192-15.

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ABSTRACTThe alphaviral6kgene region encodes the two structural proteins 6K protein and, due to a ribosomal frameshift event, the transframe protein (TF). Here, we characterized the role of the6kproteins in the arthritogenic alphavirus Ross River virus (RRV) in infected cells and in mice, using a novel6kin-frame deletion mutant. Comprehensive microscopic analysis revealed that the6kproteins were predominantly localized at the endoplasmic reticulum of RRV-infected cells. RRV virions that lack the6kproteins 6K and TF [RRV-(Δ6K)] were more vulnerable to changes in pH, and the corresponding virus h

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Pezzi, Laura, Ramona Moegling, Cécile Baronti, et al. "Low capacity for molecular detection of Alphaviruses other than Chikungunya virus in 23 European laboratories, March 2022." PLOS ONE 20, no. 2 (2025): e0318602. https://doi.org/10.1371/journal.pone.0318602.

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Alphaviruses comprise over 30 identified species spread worldwide and carry a large global health burden. With vector expansion occurring in and around Europe, it is anticipated this burden will increase. Therefore, regular assessment of the diagnostic capabilities in Europe is important, e.g., by conducting external quality assessments (EQAs). Here we evaluated molecular detection of alphaviruses in expert European laboratories by conducting an EQA in March 2022. Molecular panels included 15 samples: nine alphaviruses, Barmah Forest virus (BFV), chikungunya virus (CHIKV), Eastern equine encep

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Linn, May La, L. Mateo, J. Gardner, and A. Suhrbier. "Alphavirus-Specific Cytotoxic T Lymphocytes Recognize a Cross-Reactive Epitope from the Capsid Protein and Can Eliminate Virus from Persistently Infected Macrophages." Journal of Virology 72, no. 6 (1998): 5146–53. http://dx.doi.org/10.1128/jvi.72.6.5146-5153.1998.

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ABSTRACT Persistent alphavirus infections in synovial and neural tissues are believed to be associated with chronic arthritis and encephalitis, respectively, and represent likely targets for CD8+ αβ cytotoxic T lymphocytes (CTL). Here we show that the capsid protein is a dominant target for alphavirus-specific CTL in BALB/c mice and that capsid-specific CTL from these mice recognize anH-2Kd restricted epitope, QYSGGRFTI. This epitope lies in the highly conserved region of the capsid protein, and QYSGGRFTI-specific CTL were cross reactive across a range of Old World alphaviruses. In vivo the ac

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Cappuccio, Lucie, and Carine Maisse. "Infection of Mammals and Mosquitoes by Alphaviruses: Involvement of Cell Death." Cells 9, no. 12 (2020): 2612. http://dx.doi.org/10.3390/cells9122612.

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Alphaviruses, such as the chikungunya virus, are emerging and re-emerging viruses that pose a global public health threat. They are transmitted by blood-feeding arthropods, mainly mosquitoes, to humans and animals. Although alphaviruses cause debilitating diseases in mammalian hosts, it appears that they have no pathological effect on the mosquito vector. Alphavirus/host interactions are increasingly studied at cellular and molecular levels. While it seems clear that apoptosis plays a key role in some human pathologies, the role of cell death in determining the outcome of infections in mosquit

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Herrero, Lara J., Suan-Sin Foo, Kuo-Ching Sheng, et al. "Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease." Journal of Virology 89, no. 15 (2015): 8063–76. http://dx.doi.org/10.1128/jvi.00224-15.

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ABSTRACTArthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) cause large-scale epidemics of severe musculoskeletal disease and have been progressively expanding their global distribution. Since its introduction in July 2014, CHIKV now circulates in the United States. The hallmark of alphavirus disease is crippling pain and inflammation of the joints, a similar immunopathology to rheumatoid arthritis. The use of glycans as novel therapeutics is an area of research that has increased in recent years. Here, we describe the promising therapeutic potential of the

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Ventoso, Iván, Juan José Berlanga, René Toribio, and Irene Díaz-López. "Translational Control of Alphavirus–Host Interactions: Implications in Viral Evolution, Tropism and Antiviral Response." Viruses 16, no. 2 (2024): 205. http://dx.doi.org/10.3390/v16020205.

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Alphaviruses can replicate in arthropods and in many vertebrate species including humankind, but only in vertebrate cells do infections with these viruses result in a strong inhibition of host translation and transcription. Translation shutoff by alphaviruses is a multifactorial process that involves both host- and virus-induced mechanisms, and some of them are not completely understood. Alphavirus genomes contain cis-acting elements (RNA structures and dinucleotide composition) and encode protein activities that promote the translational and transcriptional resistance to type I IFN-induced an

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Tan, Yaw Bia, Laura Sandra Lello, Xin Liu, et al. "Crystal structures of alphavirus nonstructural protein 4 (nsP4) reveal an intrinsically dynamic RNA-dependent RNA polymerase fold." Nucleic Acids Research 50, no. 2 (2022): 1000–1016. http://dx.doi.org/10.1093/nar/gkab1302.

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Abstract Alphaviruses such as Ross River virus (RRV), chikungunya virus (CHIKV), Sindbis virus (SINV), and Venezuelan equine encephalitis virus (VEEV) are mosquito-borne pathogens that can cause arthritis or encephalitis diseases. Nonstructural protein 4 (nsP4) of alphaviruses possesses RNA-dependent RNA polymerase (RdRp) activity essential for viral RNA replication. No 3D structure has been available for nsP4 of any alphaviruses despite its importance for understanding alphaviral RNA replication and for the design of antiviral drugs. Here, we report crystal structures of the RdRp domain of ns

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Azar, Sasha R., Rafael K. Campos, Nicholas A. Bergren, Vidyleison N. Camargos, and Shannan L. Rossi. "Epidemic Alphaviruses: Ecology, Emergence and Outbreaks." Microorganisms 8, no. 8 (2020): 1167. http://dx.doi.org/10.3390/microorganisms8081167.

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Over the past century, the emergence/reemergence of arthropod-borne zoonotic agents has been a growing public health concern. In particular, agents from the genus Alphavirus pose a significant risk to both animal and human health. Human alphaviral disease presents with either arthritogenic or encephalitic manifestations and is associated with significant morbidity and/or mortality. Unfortunately, there are presently no vaccines or antiviral measures approved for human use. The present review examines the ecology, epidemiology, disease, past outbreaks, and potential to cause contemporary outbre

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Saha, Amrita, Badri Narayan Acharya, Manmohan Parida, Nandita Saxena, Jaya Rajaiya, and Paban Kumar Dash. "Identification of 2,4-Diaminoquinazoline Derivative as a Potential Small-Molecule Inhibitor against Chikungunya and Ross River Viruses." Viruses 15, no. 11 (2023): 2194. http://dx.doi.org/10.3390/v15112194.

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Alphaviruses are serious zoonotic threats responsible for significant morbidity, causing arthritis or encephalitis. So far, no licensed drugs or vaccines are available to combat alphaviral infections. About 300,000 chikungunya virus (CHIKV) infections have been reported in 2023, with more than 300 deaths, including reports of a few cases in the USA as well. The discovery and development of small-molecule drugs have been revolutionized over the last decade. Here, we employed a cell-based screening approach using a series of in-house small-molecule libraries to test for their ability to inhibit

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Montgomery, Stephanie A., Peter Berglund, Clayton W. Beard, and Robert E. Johnston. "Ribosomal Protein S6 Associates with Alphavirus Nonstructural Protein 2 and Mediates Expression from Alphavirus Messages." Journal of Virology 80, no. 15 (2006): 7729–39. http://dx.doi.org/10.1128/jvi.00425-06.

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ABSTRACT Although alphaviruses dramatically alter cellular function within hours of infection, interactions between alphaviruses and specific host cellular proteins are poorly understood. Although the alphavirus nonstructural protein 2 (nsP2) is an essential component of the viral replication complex, it also has critical auxiliary functions that determine the outcome of infection in the host. To gain a better understanding of nsP2 function, we sought to identify cellular proteins with which Venezuelan equine encephalitis virus nsP2 interacted. We demonstrate here that nsP2 associates with rib

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Masika, Moses Muia, Essi M. Korhonen, Teemu Smura, et al. "Serological Evidence of Exposure to Onyong-Nyong and Chikungunya Viruses in Febrile Patients of Rural Taita-Taveta County and Urban Kibera Informal Settlement in Nairobi, Kenya." Viruses 14, no. 6 (2022): 1286. http://dx.doi.org/10.3390/v14061286.

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Several alphaviruses, such as chikungunya (CHIKV) and Onyong-nyong (ONNV), are endemic in Kenya and often cause outbreaks in different parts of the country. We assessed the seroprevalence of alphaviruses in patients with acute febrile illness in two geographically distant areas in Kenya with no previous record of alphavirus outbreaks. Blood samples were collected from febrile patients in health facilities located in the rural Taita-Taveta County in 2016 and urban Kibera informal settlement in Nairobi in 2017 and tested for CHIKV IgG and IgM antibodies using an in-house immunofluorescence assay

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Thibodeaux, Brett A., Nathan M. Liss, Amanda N. Panella, and John T. Roehrig. "Development of a Human-Murine Chimeric Immunoglobulin M for Use in the Serological Detection of Human Alphavirus Antibodies." Clinical and Vaccine Immunology 18, no. 12 (2011): 2181–82. http://dx.doi.org/10.1128/cvi.05269-11.

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ABSTRACTDiagnosis of human alphaviral infections relies on serological techniques, such as the immunoglobulin M antibody capture–enzyme-linked immunosorbent assay (MAC-ELISA). We have humanized the alphavirus broadly cross-reactive murine monoclonal antibody 1A4B-6 to create a reagent capable of replacing human positive sera in the MAC-ELISA for diagnosis of human alphaviral infections.

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Zeng, Xiancheng, Suchetana Mukhopadhyay, and Charles L. Brooks. "Residue-level resolution of alphavirus envelope protein interactions in pH-dependent fusion." Proceedings of the National Academy of Sciences 112, no. 7 (2015): 2034–39. http://dx.doi.org/10.1073/pnas.1414190112.

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Alphavirus envelope proteins, organized as trimers of E2–E1 heterodimers on the surface of the pathogenic alphavirus, mediate the low pH-triggered fusion of viral and endosomal membranes in human cells. The lack of specific treatment for alphaviral infections motivates our exploration of potential antiviral approaches by inhibiting one or more fusion steps in the common endocytic viral entry pathway. In this work, we performed constant pH molecular dynamics based on an atomic model of the alphavirus envelope with icosahedral symmetry. We have identified pH-sensitive residues that cause the lar

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Atkins, Gregory J. "The Pathogenesis of Alphaviruses." ISRN Virology 2013 (December 4, 2013): 1–22. http://dx.doi.org/10.5402/2013/861912.

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Alphaviruses are enveloped single-stranded positive sense RNA viruses of the family Togaviridae. The genus alphavirus contains nine viruses, which are of medical, theoretical, or economic importance, and which will be considered. Sindbis virus (SINV) and Semliki Forest (SFV), although of some medical importance, have largely been studied as models of viral pathogenicity. In mice, SINV and SFV infect neurons in the central nervous system and virulent strains induce lethal encephalitis, whereas avirulent strains of SFV induce demyelination. SFV infects the developing foetus and can be teratogeni

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Sherman, Michael B., and Scott C. Weaver. "Structure of the Recombinant Alphavirus Western Equine Encephalitis Virus Revealed by Cryoelectron Microscopy." Journal of Virology 84, no. 19 (2010): 9775–82. http://dx.doi.org/10.1128/jvi.00876-10.

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ABSTRACT Western equine encephalitis virus (WEEV; Togaviridae, Alphavirus) is an enveloped RNA virus that is typically transmitted to vertebrate hosts by infected mosquitoes. WEEV is an important cause of viral encephalitis in humans and horses in the Americas, and infection results in a range of disease, from mild flu-like illnesses to encephalitis, coma, and death. In addition to spreading via mosquito vectors, human WEEV infections can potentially occur directly via aerosol transmission. Due to its aerosol infectivity and virulence, WEEV is thus classified as a biological safety level 3 (BS

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Lantz, Alyssa M., and Victoria K. Baxter. "Neuropathogenesis of Old World Alphaviruses: Considerations for the Development of Medical Countermeasures." Viruses 17, no. 2 (2025): 261. https://doi.org/10.3390/v17020261.

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Chikungunya virus (CHIKV) and other alphaviruses that primarily induce arthritogenic disease in humans, known as “Old World” alphaviruses, present an emerging public health concern as geographic ranges of mosquito vectors expand due to climate change. While a vaccine against CHIKV has recently been approved by several countries in North America and Europe, access to effective preventative countermeasures against disease induced by Old World alphaviruses remains elusive for the most vulnerable populations. Furthermore, treatment options continue to be limited to supportive care. Atypical neurol

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Treffers, Emmely E., Ali Tas, Florine E. M. Scholte, et al. "The alphavirus nonstructural protein 2 NTPase induces a host translational shut-off through phosphorylation of eEF2 via cAMP-PKA-eEF2K signaling." PLOS Pathogens 19, no. 2 (2023): e1011179. http://dx.doi.org/10.1371/journal.ppat.1011179.

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Chikungunya virus (CHIKV) is a reemerging alphavirus. Since 2005, it has infected millions of people during outbreaks in Africa, Asia, and South/Central America. CHIKV replication depends on host cell factors at many levels and is expected to have a profound effect on cellular physiology. To obtain more insight into host responses to infection, stable isotope labeling with amino acids in cell culture and liquid chromatography-tandem mass spectrometry were used to assess temporal changes in the cellular phosphoproteome during CHIKV infection. Among the ~3,000 unique phosphorylation sites analyz

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Torzyk, Karolina, Marcin Skoreński, and Marcin Sieńczyk. "ZNACZENIE AKTYWNOŚCI PROTEAZY KAPSYDOWEJ CP W ROZWOJU INFEKCJI ALFAWIRUSOWYCH." Wiadomości Chemiczne 76, no. 5 (2022): 309–21. https://doi.org/10.53584/wiadchem.2022.5.3.

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Alphaviruses belong to the worldwide distributed Togaviridae family and Alphavirus genus. They are spherical, enveloped, single-stranded RNA arthropod- borne viruses. Alphaviruses are mostly transmitted by mosquitoes (Aedes spp. and Anopheles spp.) and are geographically distributed in restricted areas where appropriate vectors are present (Fig.1.). The most recognized members of this genus are Sindbis (SINV), Semliki Forest (SFV), Venezuelan equine encephalitis (VEEV), Ross River (RRV), and Chikungunya (CHIKV) viruses. Alphaviruses are infection agents for humans and many animals. Clinically,

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Desprès, Philippe. "Alphavirus." EMC - Biologie Médicale 1, no. 2 (2006): 1. https://doi.org/10.1016/s0000-0000(03)47595-5.

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Basore, Katherine, James T. Earnest, Michael S. Diamond, and Daved H. Fremont. "Structural characterization of broadly neutralizing alphavirus antibodies." Journal of Immunology 200, no. 1_Supplement (2018): 126.33. http://dx.doi.org/10.4049/jimmunol.200.supp.126.33.

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Abstract Mayaro is a mosquito-borne single-stranded positive RNA alphavirus endemic to tropical regions of South America. It is closely related to other arthritogenic alphaviruses, such as Chikungunya, Semliki Forest, Ross River, and Sindbis viruses. Although there are currently no available vaccines or therapies for alphaviruses, previous studies demonstrate that cross-protection between different alphaviruses could be mediated by antibodies that map to conserved epitopes. For example, a class of monoclonal antibodies against Chikungunya were recently shown to neutralize other alphaviruses by

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Sousa, Ivanildo P., Carlos A. M. Carvalho, and Andre M. O. Gomes. "Current Understanding of the Role of Cholesterol in the Life Cycle of Alphaviruses." Viruses 13, no. 1 (2020): 35. http://dx.doi.org/10.3390/v13010035.

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Enveloped viruses rely on different lipid classes present in cell membranes to accomplish several steps of their life cycle in the host. Particularly for alphaviruses, a medically important group of arboviruses, which are part of the Togaviridae family, cholesterol seems to be a critical lipid exploited during infection, although its relevance may vary depending on which stage of the virus life cycle is under consideration and whether infection takes place in vertebrate or invertebrate hosts. In this review, the role of cholesterol in both early and late events of alphavirus infection and how

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Garmashova, Natalia, Rodion Gorchakov, Eugenia Volkova, Slobodan Paessler, Elena Frolova, and Ilya Frolov. "The Old World and New World Alphaviruses Use Different Virus-Specific Proteins for Induction of Transcriptional Shutoff." Journal of Virology 81, no. 5 (2006): 2472–84. http://dx.doi.org/10.1128/jvi.02073-06.

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ABSTRACT Alphaviruses are widely distributed throughout the world. During the last few thousand years, the New World viruses, including Venezuelan equine encephalitis virus (VEEV) and eastern equine encephalitis virus (EEEV), evolved separately from those of the Old World, i.e., Sindbis virus (SINV) and Semliki Forest virus (SFV). Nevertheless, the results of our study indicate that both groups have developed the same characteristic: their replication efficiently interferes with cellular transcription and the cell response to virus replication. Transcriptional shutoff caused by at least two of

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Ahola, Tero, Pekka Kujala, Minna Tuittila, et al. "Effects of Palmitoylation of Replicase Protein nsP1 on Alphavirus Infection." Journal of Virology 74, no. 15 (2000): 6725–33. http://dx.doi.org/10.1128/jvi.74.15.6725-6733.2000.

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ABSTRACT The membrane-associated alphavirus RNA replication complex contains four virus-encoded subunits, the nonstructural proteins nsP1 to nsP4. Semliki Forest virus (SFV) nsP1 is hydrophobically modified by palmitoylation of cysteines 418 to 420. Here we show that Sindbis virus nsP1 is also palmitoylated on the same site (cysteine 420). When mutations preventing nsP1 palmitoylation were introduced into the genomes of these two alphaviruses, the mutant viruses remained viable and replicated to high titers, although their growth was slightly delayed. The subcellular distribution of palmitoyla

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Brown, Rebecca S., Lisa Kim, and Margaret Kielian. "Specific Recognition of a Stem-Loop RNA Structure by the Alphavirus Capsid Protein." Viruses 13, no. 8 (2021): 1517. http://dx.doi.org/10.3390/v13081517.

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Alphaviruses are small enveloped viruses with positive-sense RNA genomes. During infection, the alphavirus capsid protein (Cp) selectively packages and assembles with the viral genomic RNA to form the nucleocapsid core, a process critical to the production of infectious virus. Prior studies of the alphavirus Semliki Forest virus (SFV) showed that packaging and assembly are promoted by Cp binding to multiple high affinity sites on the genomic RNA. Here, we developed an in vitro Cp binding assay based on fluorescently labeled RNA oligos. We used this assay to explore the RNA sequence and structu

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Heise, Mark T., Dennis A. Simpson, and Robert E. Johnston. "Sindbis-Group Alphavirus Replication in Periosteum and Endosteum of Long Bones in Adult Mice." Journal of Virology 74, no. 19 (2000): 9294–99. http://dx.doi.org/10.1128/jvi.74.19.9294-9299.2000.

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ABSTRACT Several alphaviruses, including the Sindbis-group viruses, Ross River virus, O'nyong-nyong virus, and Chikungunya virus, are associated with outbreaks of acute and persistent arthralgia and arthritis in humans. Mechanisms underlying alphavirus-induced arthralgia and arthritis are not clearly understood, though direct viral replication within or around the affected joints is thought to contribute to disease. S.A.AR86 is a Sindbis-group alphavirus closely related to the arthralgia-associated Ockelbo and GirdwoodS.A viruses. Following inoculation with S.A.AR86 derived from a molecular cl

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Thibodeaux, Brett A., Amanda N. Panella, and John T. Roehrig. "Development of Human-Murine Chimeric Immunoglobulin G for Use in the Serological Detection of Human Flavivirus and Alphavirus Antibodies." Clinical and Vaccine Immunology 17, no. 10 (2010): 1617–23. http://dx.doi.org/10.1128/cvi.00097-10.

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ABSTRACT Diagnosis of human arboviral infections relies heavily on serological techniques such as the immunoglobulin M (IgM) antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and the indirect IgG ELISA. Broad application of these assays is hindered by the lack of standardized positive human control sera that react with a wide variety of flaviviruses (e.g., dengue, West Nile, yellow fever, Japanese encephalitis, Saint Louis encephalitis, and Powassan viruses), or alphaviruses (e.g., Eastern equine encephalitis, Western equine encephalitis, Venezuelan equine encephalitis, and chikun

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Sokoloski, K. J., K. C. Haist, T. E. Morrison, S. Mukhopadhyay, and R. W. Hardy. "Noncapped Alphavirus Genomic RNAs and Their Role during Infection." Journal of Virology 89, no. 11 (2015): 6080–92. http://dx.doi.org/10.1128/jvi.00553-15.

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ABSTRACTAlphaviruses are enveloped positive-sense RNA viruses that exhibit a wide host range consisting of vertebrate and invertebrate species. Previously we have reported that the infectivity of Sindbis virus (SINV), the model alphavirus, was largely a function of the cell line producing the viral particles. Mammalian-cell-derived SINV particles, on average, exhibit a higher particle-to-PFU ratio than mosquito cell-derived SINV particles. Nevertheless, the outcome of nonproductive infection, the molecular traits that determine particle infectivity and the biological importance of noninfectiou

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