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Production and function of the cytoplasmic deproteinized relaxed circular DNA of hepadnaviruses.

ABSTRACT: Removal of genome-bound viral DNA polymerase ought to be an essential step in the formation of hepadnavirus covalently closed circular DNA (cccDNA). We previously demonstrated that deproteinized (DP) relaxed circular DNA (rcDNA) of hepatitis B virus (HBV) existed in both the cytoplasm and nuclei of infected cells and the vast majority of cytoplasmic DP rcDNA was associated with DNase I-permeable nucleocapsids. In our efforts to investigate the role of the cytoplasmic DP rcDNA in cccDNA formation, we demonstrated that rcDNA deproteinization could occur in an endogenous DNA polymerase reaction with either virion-derived or intracellular nucleocapsids. As observed in the cytoplasm of virally infected cells, in vitro deproteinization requires the maturation of plus-strand DNA and results in changes in nucleocapsid structure that render the DP rcDNA susceptible to DNase I digestion. Remarkably, we found that the cytoplasmic DP rcDNA-containing nucleocapsids could be selectively immunoprecipitated with an antibody against the carboxyl-terminal peptide of HBV core protein and are associated with cellular nuclear transport receptors karyopherin-alpha and -beta. Moreover, transfection of small interfering RNA targeting karyopherin-beta1 mRNA or expression of a dominant-negative karyopherin-beta1 in a stable cell line supporting HBV replication resulted in the accumulation of DP rcDNA in cytoplasm and reduction of nuclear DP rcDNA and cccDNA. Our results thus favor a hypothesis that completion of plus-strand DNA synthesis triggers the genomic DNA deproteinization and structural changes of nucleocapsids, which leads to the exposure of nuclear localization signals in the C terminus of core protein and mediates the nuclear transportation of DP rcDNA via interaction with karyopherin-alpha and -beta.

SUBMITTER: Guo H

PROVIDER: S-EPMC2798433 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Production and function of the cytoplasmic deproteinized relaxed circular DNA of hepadnaviruses.

Guo Haitao H Mao Richeng R Block Timothy M TM Guo Ju-Tao JT

Journal of virology 20100101 1

Removal of genome-bound viral DNA polymerase ought to be an essential step in the formation of hepadnavirus covalently closed circular DNA (cccDNA). We previously demonstrated that deproteinized (DP) relaxed circular DNA (rcDNA) of hepatitis B virus (HBV) existed in both the cytoplasm and nuclei of infected cells and the vast majority of cytoplasmic DP rcDNA was associated with DNase I-permeable nucleocapsids. In our efforts to investigate the role of the cytoplasmic DP rcDNA in cccDNA formation ...[more]

PMID: 19864387

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Project description:BackgroundTo assess if physical distancing measures to control the COVID-19 pandemic can be relaxed, one of the key indicators used is the reproduction number R. Many developing countries, however, have limited capacities to estimate R accurately. This study aims to demonstrate how health production function can be used to assess the state of COVID-19 transmission and to determine a risk-based relaxation policy.MethodsThe author employs a simple "bridge" between epidemiological models and production economics to establish the cumulative number of COVID-19 cases as a short-run total product function and to derive the corresponding marginal product, average product, and production elasticity. Three crucial dates defining the states of transmission, labelled red, yellow, and green zones, are determined. Relaxation policy is illogical in the "red zone" and is not recommended in the "yellow zone". In the "green zone", relaxation can be considered. The Bayesian probability of near term's daily cases meeting a policy target is computed. The method is applied to France, Germany, Italy, the UK, and the US, and to Indonesia as an example of application in developing countries.ResultsThis study uses data from the WHO COVID-19 Dashboard, beginning from the first recording date for each country until February 28, 2021. As of June 30, 2020, France, Germany, Italy, and the UK had arrived at the "green zone" but with a high risk of transmission re-escalations. In the following weeks, their production elasticities were rising, giving a signal of accelerated transmissions. The signal was corroborated by these countries' rising cases, making them leaving the "green zone" in the later months. By February 28, 2021, the UK had returned to the "green zone", France, Germany, and Italy were still in the "yellow zone", while the US reached the "green zone" at a very high number of cases. Despite being in the "red zone", Indonesia relaxed its distancing measures, causing a sharp rise of cases.ConclusionsHealth production function can show the state of COVID-19 transmission. A rising production elasticity gives an early warning of transmission escalations. The elasticity is a useful parameter for risk-based relaxation policy.

Dataset Information

Production and function of the cytoplasmic deproteinized relaxed circular DNA of hepadnaviruses.

Publications

Production and function of the cytoplasmic deproteinized relaxed circular DNA of hepadnaviruses.

Similar Datasets

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