Inhibition of nucleo-cytoplasmic trafficking by RNA viruses: targeting the nuclear pore complex

Abstract

Analysis of virus-host interactions has revealed a variety of ways in which viruses utilize and/or alter host functions in an effort to facilitate efficient replication. Recent work has suggested that certain RNA viruses that replicate in the cytoplasm disrupt the normal trafficking of cellular RNAs and proteins within the host cell. This review will examine the recent evidence showing that poliovirus and vesicular stomatitis virus (VSV) can inhibit nucleo-cytoplasmic transport within cells. Interestingly, the data indicate that inhibition by both viruses involves targeting components of the nuclear pore complex (NPC). Following this, several possible explanations for why viruses might disrupt nucleo-cytoplasmic transport are discussed. Finally, the possibility that disruption of nucleo-cytoplasmic trafficking may be a more common feature of RNA virus-host interactions than previously thought is examined.

Inhibition of U snRNP assembly by a virus-encoded proteinase

“…They hypothesized that the differential effects were due to nuclear import of endogenous Sm proteins in the absence of core formation and the potential saturation of this alternative import pathway by GFP-SmB (Shpargel and Matera 2005). Poliovirus is known to inhibit multiple nuclear import pathways including the importin-␣-mediated classical pathway (for review, see Gustin 2003). One hypothesis for the specific effects of poliovirus on the localization of Sm proteins is that the importin-␤-mediated nuclear import of snRNPs occurs during infection, while the import of individual Sm proteins is blocked.…”

Differential effect of acute and persistent Junín virus infections on the nucleo-cytoplasmic trafficking and expression of heterogeneous nuclear ribonucleoproteins type A and B

“…Several cytoplasmic RNA viruses alter the nucleo-cytoplasmic trafficking of cellular RNA and proteins and this may facilitate viral replication and help subvert the host antiviral response (Gustin 2003;Rodriguez et al, 2003;Reid et al,These proteins have a highly conserved amino-terminal domain, which contains two tandemly repeated RNAbinding domains that are directly involved in RNA binding, and a divergent glycine-rich domain at the carboxy terminus, which is implicated in protein-protein interactions. hnRNPs A1 and A2 are known to shuttle between the nucleus and the cytoplasm and this shuttling is mediated by a sequence (M9) located near the carboxy terminus of the proteins (Shi et al, 2003).…”

“…During persistence cells remain unable to produce infectious virus, with a continuous synthesis of virus nucleoprotein (N) associated with blockage of the expression of the glycoprotein G1 and absence of cytopathic action (Ellenberg et al, 2002(Ellenberg et al, , 2004. Little is known about the cell components involved in JUNV replication during acute infection or in the establishment and maintenance of persistent infection.Several cytoplasmic RNA viruses alter the nucleo-cytoplasmic trafficking of cellular RNA and proteins and this may facilitate viral replication and help subvert the host antiviral response (Gustin 2003;Rodriguez et al, 2003;Reid et al, 2006; Frieman et al, 2007). Heterogeneous nuclear ribonucleoproteins (hnRNPs) constitute a large group of RNAbinding proteins which participate in a variety of cellular functions, including mRNA splicing, trafficking, translation and turnover.…”

Cytoplasmic translocation, aggregation, and cleavage of TDP-43 by enteroviral proteases modulate viral pathogenesis

“…[3][4][5] Although enteroviral replication takes place exclusively in the cytoplasm, viral infection has been demonstrated to lead to cytoplasmic translocation of nuclear proteins. 6 For example, heterogeneous ribonucleoprotein D (hnRNP D) has been shown to translocate from the nucleus to the cytoplasm during enteroviral infection. 5,7,8 Moreover, hnRNP D is cleaved by 3C and has an antiviral function against enteroviral infection.…”