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View article: Norepinephrine stimulates protein synthesis in astrocytes
Norepinephrine stimulates protein synthesis in astrocytes Open
Norepinephrine is a neuromodulator that can activate multiple subcellular signalling pathways to regulate various physiological responses in different cell types. In astrocytes, it is known to have a wide range of metabolic effects, includ…
View article: nsP4 Is a Major Determinant of Alphavirus Replicase Activity and Template Selectivity
nsP4 Is a Major Determinant of Alphavirus Replicase Activity and Template Selectivity Open
A key element of every virus with an RNA genome is the RNA replicase. Understanding the principles of RNA replicase formation and functioning is therefore crucial for understanding and responding to the emergence of new viruses.
View article: Interdomain Flexibility of Chikungunya Virus nsP2 Helicase-Protease Differentially Influences Viral RNA Replication and Infectivity
Interdomain Flexibility of Chikungunya Virus nsP2 Helicase-Protease Differentially Influences Viral RNA Replication and Infectivity Open
CHIKV nsP2 plays multiple roles in viral RNA replication and virus-host interactions. The helicase and protease regions of nsP2 are connected through a short linker.
View article: Cross-utilisation of template RNAs by alphavirus replicases
Cross-utilisation of template RNAs by alphavirus replicases Open
Most alphaviruses (family Togaviridae) including Sindbis virus (SINV) and other human pathogens, are transmitted by arthropods. The first open reading frame in their positive strand RNA genome encodes for the non-structural polyprotein, a …
View article: Structural and Functional Studies of Chikungunya Virus nsP2
Structural and Functional Studies of Chikungunya Virus nsP2 Open
Chikungunya virus (CHIKV) is transmitted to humans through mosquitoes and causes Chikungunya fever. Nonstructural protein 2 (nsP2) contains an N-terminal RNA helicase with both nucleotide triphosphatase and RNA triphosphatase activities, a…
View article: Bortezomib inhibits chikungunya virus replication by interfering with viral protein synthesis
Bortezomib inhibits chikungunya virus replication by interfering with viral protein synthesis Open
Chikungunya virus (CHIKV) is an alphavirus that causes a febrile illness accompanied by myalgia and arthralgia. Despite having re-emerged as a significant public health threat, there are no approved therapeutics or prophylactics for CHIKV …
View article: Sensitivity of Alphaviruses to G3BP Deletion Correlates with Efficiency of Replicase Polyprotein Processing
Sensitivity of Alphaviruses to G3BP Deletion Correlates with Efficiency of Replicase Polyprotein Processing Open
Old World alphaviruses comprise several medically relevant viruses, including chikungunya virus and Ross River virus. Recurrent outbreaks and the lack of antivirals and vaccines demand ongoing research to fight the emergence of these infec…
View article: VCP/p97 Is a Proviral Host Factor for Replication of Chikungunya Virus and Other Alphaviruses
VCP/p97 Is a Proviral Host Factor for Replication of Chikungunya Virus and Other Alphaviruses Open
The evolutionarily conserved AAA+ ATPase valosin-containing protein (VCP) was previously shown to be a proviral host factor for several viruses from different viral families such as Flaviviridae, Picornaviridae, and Herpesviridae. VCP was …
View article: Design and Use of Chikungunya Virus Replication Templates Utilizing Mammalian and Mosquito RNA Polymerase I-Mediated Transcription
Design and Use of Chikungunya Virus Replication Templates Utilizing Mammalian and Mosquito RNA Polymerase I-Mediated Transcription Open
Chikungunya virus (CHIKV) is a medically important pathogen responsible for recent large-scale epidemics. The development of efficient therapies against CHIKV has been hampered by gaps in our understanding of how nonstructural proteins (ns…
View article: Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate
Mutating chikungunya virus non‐structural protein produces potent live‐attenuated vaccine candidate Open
Currently, there are no commercially available live-attenuated vaccines against chikungunya virus (CHIKV). Here, CHIKVs with mutations in non-structural proteins (nsPs) were investigated for their suitability as attenuated CHIKV vaccines. …
View article: Structural insights into RNA recognition by the Chikungunya virus nsP2 helicase
Structural insights into RNA recognition by the Chikungunya virus nsP2 helicase Open
Chikungunya virus (CHIKV) is transmitted to humans through mosquitoes and causes Chikungunya fever. Nonstructural protein 2 (nsP2) exhibits the protease and RNA helicase activities that are required for viral RNA replication and transcript…
View article: ADP-ribosyl–binding and hydrolase activities of the alphavirus nsP3 macrodomain are critical for initiation of virus replication
ADP-ribosyl–binding and hydrolase activities of the alphavirus nsP3 macrodomain are critical for initiation of virus replication Open
Significance Alphaviruses are mosquito-borne RNA viruses that cause encephalitis, rash, and arthritis. Alphavirus nonstructural protein 3 (nsP3) has a highly conserved macrodomain that can bind and remove ADP-ribose (ADPr) residues from AD…
View article: Decreased Virulence of Ross River Virus Harboring a Mutation in the First Cleavage Site of Nonstructural Polyprotein Is Caused by a Novel Mechanism Leading to Increased Production of Interferon-Inducing RNAs
Decreased Virulence of Ross River Virus Harboring a Mutation in the First Cleavage Site of Nonstructural Polyprotein Is Caused by a Novel Mechanism Leading to Increased Production of Interferon-Inducing RNAs Open
Infection with Ross River virus (RRV) causes debilitating polyarthritis and arthralgia in individuals. Alphaviruses are highly sensitive to type I interferon (IFN). Mutations at the conserved P3 position of the cleavage site between nonstr…
View article: A Chikungunya Virus <i>trans</i> -Replicase System Reveals the Importance of Delayed Nonstructural Polyprotein Processing for Efficient Replication Complex Formation in Mosquito Cells
A Chikungunya Virus <i>trans</i> -Replicase System Reveals the Importance of Delayed Nonstructural Polyprotein Processing for Efficient Replication Complex Formation in Mosquito Cells Open
Chikungunya virus (CHIKV) is a medically important alphavirus that is transmitted by Aedes aegypti and Aedes albopictus mosquitoes. The viral replicase complex consists of four nonstructural proteins (nsPs) expressed as a polyprotein precu…
View article: Partially Uncleaved Alphavirus Replicase Forms Spherule Structures in the Presence and Absence of RNA Template
Partially Uncleaved Alphavirus Replicase Forms Spherule Structures in the Presence and Absence of RNA Template Open
Alphaviruses are positive-strand RNA viruses expressing their replicase as a polyprotein, P1234, which is cleaved to four final products, nonstructural proteins nsP1 to nsP4. The replicase proteins together with viral RNA and host factors …
View article: Design and Validation of Novel Chikungunya Virus Protease Inhibitors
Design and Validation of Novel Chikungunya Virus Protease Inhibitors Open
Chikungunya virus (CHIKV; genus Alphavirus ) is the causative agent of chikungunya fever. CHIKV replication can be inhibited by some broad-spectrum antiviral compounds; in contrast, there is very little information about compounds specific…
View article: Versatile Trans-Replication Systems for Chikungunya Virus Allow Functional Analysis and Tagging of Every Replicase Protein
Versatile Trans-Replication Systems for Chikungunya Virus Allow Functional Analysis and Tagging of Every Replicase Protein Open
Chikungunya virus (CHIKV; genus Alphavirus, family Togaviridae) has recently caused several major outbreaks affecting millions of people. There are no licensed vaccines or antivirals, and the knowledge of the molecular biology of CHIKV, cr…