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Cellular localization and effects of ectopically expressed hepatitis A virus proteins 2B, 2C, 3A and their intermediates 2BC, 3AB and 3ABC

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Abstract

In the course of hepatitis A virus (HAV) infections, the seven nonstructural proteins and their intermediates are barely detectable. Therefore, little is known about their functions and mechanisms of action. Ectopic expression of the presumably membrane-associated proteins 2B, 2C, 3A and their intermediates 2BC, 3AB and 3ABC allowed the intracellular localization of these proteins and their possible function during the replication cycle of HAV to be investigated. In this study, we used rhesus monkey kidney cells, which are commonly used for cell culture experiments, and human liver cells, which are the natural target cells. We detected specific associations of these proteins with distinct membrane compartments and the cytoskeleton, different morphological alterations of the respective structures, and specific effects on cellular functions. Besides comparable findings in both cell lines used with regard to localization and effects of the proteins examined, we also found distinct differences. The data obtained identify so far undocumented interactions with and effects of the HAV proteins investigated on cellular components, which may reflect unknown aspects of the interaction of HAV with the host cell, for example the modification of the ERGIC (ER-Golgi intermediate compartment) structure, an interaction with lipid droplets and lysosomes, and inhibition of the classical secretory pathway.

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Acknowledgments

This work was supported by Grant BFK-no. 02/803/08 of the University of Bremen, Bremen, Germany, and by the Tönjes-Vagt-Stiftung, Project XXIX, Bremen, Germany.

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  1. Erna Domsgen

    Present address: Department of Medicine Huddinge, Karolinska Institutet, Center for Infectious Medicine (CIM), Karolinska University Hospital Huddinge, F59, 141 86, Stockholm, Sweden

Authors and Affiliations

  1. Laboratory of Virus Research, University of Bremen, Leobener Straße/UFT, 28359, Bremen, Germany

    Nicole Seggewiß, Hedi Verena Kruse, Rebecca Weilandt, Erna Domsgen, Andreas Dotzauer & Dajana Paulmann

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  1. Nicole Seggewiß
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  2. Hedi Verena Kruse
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Correspondence to Dajana Paulmann.

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Funding

This study was funded by BFK of the University of Bremen, Bremen, Germany (Grant number 02/803/08), and by the Tönjes-Vagt-Stiftung, Bremen, Germany (Grant number XXIX).

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All authors declare that they have no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors.

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Seggewiß, N., Kruse, H.V., Weilandt, R. et al. Cellular localization and effects of ectopically expressed hepatitis A virus proteins 2B, 2C, 3A and their intermediates 2BC, 3AB and 3ABC. Arch Virol 161, 851–865 (2016). https://doi.org/10.1007/s00705-015-2723-5

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