Research Article: Vesicular Transport of Progeny Parvovirus Particles through ER and Golgi Regulates Maturation and Cytolysis

Date Published: September 19, 2013

Publisher: Public Library of Science

Author(s): Séverine Bär, Jean Rommelaere, Jürg P. F. Nüesch, Matthew D. Weitzman.

http://doi.org/10.1371/journal.ppat.1003605

Abstract

Progeny particles of non-enveloped lytic parvoviruses were previously shown to be actively transported to the cell periphery through vesicles in a gelsolin-dependent manner. This process involves rearrangement and destruction of actin filaments, while microtubules become protected throughout the infection. Here the focus is on the intracellular egress pathway, as well as its impact on the properties and release of progeny virions. By colocalization with cellular marker proteins and specific modulation of the pathways through over-expression of variant effector genes transduced by recombinant adeno-associated virus vectors, we show that progeny PV particles become engulfed into COPII-vesicles in the endoplasmic reticulum (ER) and are transported through the Golgi to the plasma membrane. Besides known factors like sar1, sec24, rab1, the ERM family proteins, radixin and moesin play (an) essential role(s) in the formation/loading and targeting of virus-containing COPII-vesicles. These proteins also contribute to the transport through ER and Golgi of the well described analogue of cellular proteins, the secreted Gaussia luciferase in absence of virus infection. It is therefore likely that radixin and moesin also serve for a more general function in cellular exocytosis. Finally, parvovirus egress via ER and Golgi appears to be necessary for virions to gain full infectivity through post-assembly modifications (e.g. phosphorylation). While not being absolutely required for cytolysis and progeny virus release, vesicular transport of parvoviruses through ER and Golgi significantly accelerates these processes pointing to a regulatory role of this transport pathway.

Partial Text

Egress of enveloped viruses is typically associated with the cell secretory pathway guiding the particles and/or their precursors through cellular organelles, in particular the endoplasmic reticulum (ER) and the Golgi cisternae [1]–[7]. In this regard, enveloped viruses usurp the cellular secretory machinery in order to achieve the efficient transport of progeny viruses to the plasma membrane and the maturation of precursor particles into infectious virions [8]–[14]. In contrast, non-enveloped viruses are thought to be released as mature virions through a cytolysis burst at the end of infection [15]–[17]. However, there is evidence on non-enveloped virus egress through active transport besides the major lytic pathway. A few non-enveloped lytic viruses were shown to be actively transported to the cell periphery and released prior to cell lysis. For instance SV40 was detected in intra-cytoplasmic smooth membrane vesicles and described as being released from the cell before cytopathic effects are seen [18]. Similarly, cocksackie B3 virus was found to be transferred from cell to cell through microvesicles [19]. We also recently reported that in the case of non-enveloped lytic parvoviruses that progeny virions are actively transported from the nucleus to the plasma membrane (PM) through vesicles in a gelsolin-dependent manner [20].

Progeny virion shuttling from the nucleus, the site of parvovirus replication and assembly, to the plasma membrane is an important step in virus release and cell to cell spread. The present analysis shows that the release of non-enveloped PVs is not a mere consequence of the cellular lytic burst occurring at the very end of the viral life-cycle but involves a pre-lytic active vesicular transport of virions. This transport makes virions transit through ER and Golgi, and appears to have two major implications: the maturation of progeny particles into fully infectious virions, and the induction of cytolysis with the ensuing virus spread. For this transport process, PVs usurp cellular components allowing progeny virion engulfment into COPII vesicles at the ER and moving through the Golgi to the plasma membrane under control of small Rab GTPases. This vesicular trafficking is a general feature of rodent parvoviruses as it was demonstrated for both, the mouse virus MVM and rat virus H-1PV in mouse and human cancer cells, respectively.

 

Source:

http://doi.org/10.1371/journal.ppat.1003605

 

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