Hijacking components of the cellular secretory pathway for replication of poliovirus RNA

National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-8011, USA.
Journal of Virology (Impact Factor: 4.65). 02/2007; 81(2):558-67. DOI: 10.1128/JVI.01820-06
Source: PubMed

ABSTRACT Infection of cells with poliovirus induces a massive intracellular membrane reorganization to form vesicle-like structures where viral RNA replication occurs. The mechanism of membrane remodeling remains unknown, although some observations have implicated components of the cellular secretory and/or autophagy pathways. Recently, we showed that some members of the Arf family of small GTPases, which control secretory trafficking, became membrane-bound after the synthesis of poliovirus proteins in vitro and associated with newly formed membranous RNA replication complexes in infected cells. The recruitment of Arfs to specific target membranes is mediated by a group of guanine nucleotide exchange factors (GEFs) that recycle Arf from its inactive, GDP-bound state to an active GTP-bound form. Here we show that two different viral proteins independently recruit different Arf GEFs (GBF1 and BIG1/2) to the new structures that support virus replication. Intracellular Arf-GTP levels increase approximately 4-fold during poliovirus infection. The requirement for these GEFs explains the sensitivity of virus growth to brefeldin A, which can be rescued by the overexpression of GBF1. The recruitment of Arf to membranes via specific GEFs by poliovirus proteins provides an important clue toward identifying cellular pathways utilized by the virus to form its membranous replication complex.

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Available from: Catherine Jackson, Aug 16, 2015
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    • "These pathogens each utilize Golgi-or ER-derived membrane to promote their intracellular replication. Poliovirus diverts host Golgiderived membrane to form vesicles containing viral replication complexes (Belov et al., 2007). Legionella or Brucella replicate within vacuoles containing membrane derived from the ER (Isberg et al., 2009; Hubber and Roy, 2010; von Bargen et al., 2012). "
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    • "Recent studies have provided evidence that PV and CVs generate membranes for replication by subversion of Arf1- dependent COPI vesicle formation (Belov et al., 2007, 2010; Hsu et al., 2010; Lanke et al., 2009; Teterina et al., 2011; Wessels et al., 2006a, b). PV 3A protein binds GBF1 and modulates recruitment of Arf1 effectors to favour phosphatidylinositol 4-kinase (PI4K) over COPI components . "
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    Journal of General Virology 08/2013; 94(Pt 12). DOI:10.1099/vir.0.055442-0 · 3.53 Impact Factor
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    • "Depending on the virus, different organelles may be affected but with one purpose: the production of viral replication complexes (VRCs), which serve to protect the replication machinery from host cell nucleases (Ding et al., 2004; Schwartz et al., 2004). As with poliovirus in mammalian cells (Belov et al., 2007), potyviruses appear to high-jack the early secretory pathway in order to form VRCs. One candidate for the modification of the host cell ER in the case of Tobacco Etch Virus (TEV) is a 6 kDa (53 amino acids) protein which has a putative short luminal domain (11 aa), a 19 aa transmembrane domain, and a 23 aa cytoplasmic domain (Fig. 1A). This is one of eight proteins encoded by the TEV genome (Schaad et al., 1997). "
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