Running title: Targeting virus assembly Small-Molecule Effectors of Hepatitis B Virus Capsid Assembly Give Insight Into Virus Lifecycle
نویسندگان
چکیده
word count: 203 d – current address 250 McElroy Hall Department of Veterinary Pathobiology Oklahoma State University Stillwater, Oklahoma 74078-2007 e* current address, corresponding author Adam Zlotnick Department of Biology Indiana University Simon Hall MSB, Room 220D 212 S. Hawthorne Drive Bloomington IN 47405-7003 [email protected] fax 812-856-5710 AC CE PT ED Copyright © 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved. J. Virol. doi:10.1128/JVI.01360-08 JVI Accepts, published online ahead of print on 6 August 2008 on July 0, 2017 by gest http/jvi.asm .rg/ D ow nladed fom
منابع مشابه
Small-molecule effectors of hepatitis B virus capsid assembly give insight into virus life cycle.
The relationship between the physical chemistry and biology of self-assembly is poorly understood, but it will be critical to quantitatively understand infection and for the design of antivirals that target virus genesis. Here we take advantage of heteroaryldihydropyrimidines (HAPs), which affect hepatitis B virus (HBV) assembly, to gain insight and correlate in vitro assembly with HBV replicat...
متن کاملPhase diagrams map the properties of antiviral agents directed against hepatitis B virus core assembly.
Assembly effectors are small molecules that induce inappropriate virus capsid assembly to antiviral effect. To identify attributes of hepatitis B virus (HBV) assembly effectors, assembly reaction products (normal capsid, noncapsid polymer, intermediates, and free dimeric core protein) were quantified in the presence of three experimental effectors: HAP12, HAP13, and AT-130. Effectors bound stoi...
متن کاملA heteroaryldihydropyrimidine activates and can misdirect hepatitis B virus capsid assembly.
Heteroaryldihydropyrimidines (HAPs) are a new class of antivirals inhibiting production of hepatitis B virus (HBV) virions in tissue culture. Here, we examine the effect of a representative HAP molecule, methyl 4-(2-chloro-4-fluorophenyl)-6-methyl-2-(pyridin-2-yl)-1,4-dihydropyrimidine-5-carboxylate (HAP-1), on the in vitro assembly of HBV capsid protein (Cp). HAP-1 enhances the rate and extent...
متن کاملConformational changes in the hepatitis B virus core protein are consistent with a role for allostery in virus assembly.
In infected cells, virus components must be organized at the right place and time to ensure assembly of infectious virions. From a different perspective, assembly must be prevented until all components are available. Hypothetically, this can be achieved by allosterically controlling assembly. Consistent with this hypothesis, here we show that the structure of the hepatitis B virus (HBV) core pr...
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The C-terminal domain (CTD) of Hepatitis B virus (HBV) core protein is involved in regulating multiple stages of the HBV lifecycle. CTD phosphorylation correlates with pregenomic-RNA encapsidation during capsid assembly, reverse transcription, and viral transport, although the mechanisms remain unknown. In vitro, purified HBV core protein (Cp183) binds any RNA and assembles aggressively, indepe...
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