Interactions between the Dengue Virus Polymerase NS5 and Stem-Loop A

Bujalowski, Paul J.; Bujalowski, Wlodzimierz; Choi, Kyung Hyun

doi:10.1128/jvi.00047-17

Cited by 30 publications

(28 citation statements)

References 42 publications

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“…In contrast to previous studies conducted by Gamarnik and colleagues, our EMSA confirmed the affinity of RdRp with 3′ SL and a sensitive in vitro alpha binding assay provided an apparent K d of ≈3 n m for the interaction between RdRp and SL‐TL . It should be noted that two recent studies in which affinities of DENV RdRp with a 5′‐UTR fragment containing SLA were measured in solution yielded K d values ranging from 53 n m to 142 n m …”

Section: Numerous Genomic Rna Structures Are Involved In Replicationcontrasting

confidence: 63%

Flavors of Flaviviral RNA Structure: towards an Integrated View of RNA Function from Translation through Encapsidation

et al. 2019

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For many viruses, RNA is the holder of genetic information and serves as the template for both replication and translation. While host and viral proteins play important roles in viral decision‐making, the extent to which viral RNA (vRNA) actively participates in translation and replication might be surprising. Here, the focus is on flaviviruses, which include common human scourges such as dengue, West Nile, and Zika viruses, from an RNA‐centric viewpoint. In reviewing more recent findings, an attempt is made to fill knowledge gaps and revisit some canonical views of vRNA structures involved in replication. In particular, alternative views are offered on the nature of the flaviviral promoter and genome cyclization, and the feasibility of refining in vitro‐derived models with modern RNA probing and sequencing methods is pointed out. By tracing vRNA structures from translation through encapsidation, a dynamic molecule closely involved in the self‐regulation of viral replication is revealed.

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Section: Numerous Genomic Rna Structures Are Involved In Replicationcontrasting

confidence: 63%

Flavors of Flaviviral RNA Structure: towards an Integrated View of RNA Function from Translation through Encapsidation

et al. 2019

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“…In these experiments the relative fluorescence change is defined as Δ F obs = F i / F 0 , where F i is the fluorescence intensity at a given titration point and F 0 is the initial value of the fluorescence of the sample. Both F 0 and F i were corrected for background fluorescence at the applied excitation wavelength ( 28 ).…”

Section: Methodsmentioning

confidence: 99%

NMR structure of a vestigial nuclease provides insight into the evolution of functional transitions in viral dsDNA packaging motors

Mahler

Bujalowski

Mao

et al. 2020

Nucleic Acids Research

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Double-stranded DNA viruses use ATP-powered molecular motors to package their genomic DNA. To ensure efficient genome encapsidation, these motors regulate functional transitions between initiation, translocation, and termination modes. Here, we report structural and biophysical analyses of the C-terminal domain of the bacteriophage phi29 ATPase (CTD) that suggest a structural basis for these functional transitions. Sedimentation experiments show that the inter-domain linker in the full-length protein promotes oligomerization and thus may play a role in assembly of the functional motor. The NMR solution structure of the CTD indicates it is a vestigial nuclease domain that likely evolved from conserved nuclease domains in phage terminases. Despite the loss of nuclease activity, fluorescence binding assays confirm the CTD retains its DNA binding capabilities and fitting the CTD into cryoEM density of the phi29 motor shows that the CTD directly binds DNA. However, the interacting residues differ from those identified by NMR titration in solution, suggesting that packaging motors undergo conformational changes to transition between initiation, translocation, and termination. Taken together, these results provide insight into the evolution of functional transitions in viral dsDNA packaging motors.

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“…92 The SLA serves as a promoter for viral replication, likely through direct recruitment of the RdRp (NS5). 93–95 Downstream of the SLA is a uridine-rich region that acts as a spacer between the two 5′ terminal domains and enhances viral replication. 94 The second domain of the 5′ terminal region extends from the 5′UTR into the C ORF.…”

Section: Biochemistry and Molecular Biology Of Flavivirusesmentioning

confidence: 99%

Biochemistry and Molecular Biology of Flaviviruses

et al. 2018

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Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA–protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.

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Interactions between the Dengue Virus Polymerase NS5 and Stem-Loop A

Cited by 30 publications

References 42 publications

Flavors of Flaviviral RNA Structure: towards an Integrated View of RNA Function from Translation through Encapsidation

Flavors of Flaviviral RNA Structure: towards an Integrated View of RNA Function from Translation through Encapsidation

NMR structure of a vestigial nuclease provides insight into the evolution of functional transitions in viral dsDNA packaging motors

Biochemistry and Molecular Biology of Flaviviruses

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