Viral security proteins: counteracting host defences

Agol, Vadim I.; Gmyl, Anatoly P.

doi:10.1038/nrmicro2452

Cited by 68 publications

(79 citation statements)

References 131 publications

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“…We found evidence for both apoptosis and necrosis amongst infected cells regardless of the EV type, in agreement with data indicating a competition between cell death pathways and picornavirus replication (Agol & Gmyl, 2010). We also observed disruption of the actin cytoskeleton network and that of intercellular junctions as evidenced by the rounding of infected cells.…”

Section: Impairment Of the Bbb By Enterovirusessupporting

confidence: 78%

Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood–brain barrier

Volle

Archimbaud

Couraud

et al. 2015

Journal of General Virology

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Human cerebral microvascular endothelial cells (hCMEC/D3 cell line) form a steady polarized barrier when cultured in vitro on a permeable membrane. Their susceptibility to enterovirus (EV) strains was analysed to investigate how these viruses may cross the blood-brain barrier. A sample of 88 virus strains was selected on phylogenetic features amongst 43 epidemiologically relevant types of the four EV species A-D. The EV-A71 genome was replicated at substantial rates, whilst the infectious virus was released at extremely low but sustained rates at both barrier sides for at least 4 days. EV-A71 antigens were detected in a limited number of cells. The properties of the endothelial barrier (structure and permeability) remained intact throughout infection. The chronic EV-A71 infection was in sharp contrast to the productive infection of cytolytic EVs (e.g. echoviruses E-6 and E-30). The hCMEC/D3 barriers infected with the latter EVs exhibited elevated proportions of apoptotic and necrotic cells, which resulted in major injuries to the endothelial barriers with a dramatic increase of paracellular permeability and virus crossing to the abluminal side. The following intracellular rearrangements were also seen: early destruction of the actin cytoskeleton, remodelling of intracellular membranes and reorganization of the mitochondrion network in a small cluster near the perinuclear space.

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Section: Impairment Of the Bbb By Enterovirusessupporting

confidence: 78%

Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood–brain barrier

Volle

Archimbaud

Couraud

et al. 2015

Journal of General Virology

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“…In FMDV replication, the 2BC polypeptide, rather than 3A or 2B, is responsible for the blockage of ER-to-Golgi apparatus traffic (43,44). In view of the observed heterogeneity in protein structure of these small picornavirus proteins, it has been concluded that the mechanisms by which they exert their inhibition of protein secretion must be different (1,12). On the basis of several studies reporting inhibition of protein secretion by picornaviruses or picornavirus nonstructural proteins (8,22,23,47,67), we expected that GLuc would not be released from PV-GLuc-infected cells.…”

Section: Discussionmentioning

confidence: 99%

“…A failure to block protein transport by 3A or other small enterovirus proteins corresponding to those of PV has been reported for many picornaviruses, such as hepatitis A virus, enterovirus 71, Theiler's virus, and rhinovirus 14 (1,12). In FMDV replication, the 2BC polypeptide, rather than 3A or 2B, is responsible for the blockage of ER-to-Golgi apparatus traffic (43,44).…”

Section: Discussionmentioning

confidence: 99%

“…Since in vivo poliovirus RNA replication is stringently dependent upon translation in cis (33,49) and because encapsidation, in turn, requires RNA replication in cis (1,33,34,45,71), it is difficult to design reliable experiments that distinguish between defects in viral replication and morphogenesis.…”

mentioning

confidence: 99%

“…Most dramatic are the inhibition of cellular protein and cellular RNA synthesis, the rearrangement of existing cytoplasmic membranous structures, and the de novo synthesis of new vesicles (6, 9-11, 18, 55, 56, 58). In addition, the viruses induce a large number of changes in the host cell that are designed to favor viral replication and, at the same time, paralyze host cell defense mechanisms (1,42,56).…”

mentioning

confidence: 99%

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Evolution of Poliovirus Defective Interfering Particles Expressing Gaussia Luciferase

Song

Paul

Wimmer

2012

J Virol

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Polioviruses (PVs) carrying a reporter gene are useful tools for studies of virus replication, particularly if the viral chimeras contain the polyprotein that provides all of the proteins necessary for a complete replication cycle. Replication in HeLa cells of a previously constructed poliovirus expressing the gene for Renilla luciferase (RLuc) fused to the N terminus of the polyprotein H 2 NRLuc-P1-P2-P3-COOH (P1, structural domain; P2 and P3, nonstructural domains) led to the deletion of RLuc after only one passage. Here we describe a novel poliovirus chimera that expresses Gaussia luciferase (GLuc) inserted into the polyprotein between P1 and P2 (N 2 H-P1-GLuc-P2-P3-COOH). This chimera, termed PV-GLuc, replicated to 10% of wild-type yield. The reporter signal was fully retained for three passages and then gradually lost. After six passages the signal was barely detectable. On further passages, however, the GLuc signal reappeared, and after eight passages it had reached the same levels observed with the original PV-GLuc at the first passage. We demonstrated that this surprising observation was due to coevolution of defective interfering (DI) particles that had lost part or all of the capsid coding sequence (⌬P1-GLuc-P2-P3) and wild-type-like viruses that had lost the GLuc sequence (P1-P2-P3). When used at low passage, PV-GLuc is an excellent tool for studying aspects of genome replication and morphogenesis. The GLuc protein was secreted from mammalian cells but, in agreement with published data, was not secreted from PV-GLuc-infected cells due to poliovirus-induced inhibition of cellular protein secretion. Published evidence indicates that individual expression of enterovirus polypeptide 3A, 2B, or 2BC in COS-1 cells strongly inhibits host protein secretion. In HeLa cells, however, expression of none of the poliovirus polypeptides, either singly or in pairs, inhibited GLuc secretion. Thus, inhibition of GLuc secretion in PV-infected HeLa cells is likely a result of the interaction between several viral and cellular proteins that are different from those in COS-1 cells.

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Infection of human islets of langerhans with two strains of coxsackie B virus serotype 1: Assessment of virus replication, degree of cell death and induction of genes involved in the innate immunity pathway

Anagandula

Richardson

Oberste

et al. 2013

Journal of Medical Virology

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Type 1 diabetes mellitus is believed to be triggered, in part, by one or more environmental factors and human enteroviruses (HEVs) are among the candidates. Therefore, this study has examined whether two strains of HEV may differentially affect the induction of genes involved in pathways leading to the synthesis of islet hormones, chemokines and cytokines in isolated, highly purified, human islets. Isolated, purified human pancreatic islets were infected with strains of Coxsackievirus B1.Viral replication and the degree of CPE/islet dissociation were monitored. The expression of insulin, glucagon, CXCL10, TLR3, IF1H1, CCL5, OAS-1, IFNβ, and DDX58 was analyzed. Both strains replicated in islets but only one of strain caused rapid islet dissociation/CPE. Expression of the insulin gene was reduced during infection of islets with either viral strain but the gene encoding glucagon was unaffected. All genes analyzed which are involved in viral sensing and the development of innate immunity were induced by Coxsackie B viruses, with the notable exception of TLR3. There was no qualitative difference in the expression pattern between each strain but the magnitude of the response varied between donors. The lack of virus induced expression of TLR3, together with the differential regulation of IF1H1, OAS1 and IFNβ, (each of which has polymorphic variants influence the predisposition to type 1 diabetes), that might result in defective clearance of virus from islet cells. The reduced expression of the insulin gene and the unaffected expression of the gene encoding glucagon by Coxsackie B1 infection is consistent with the preferential β-cell tropism of the virus.

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Viral security proteins: counteracting host defences

Cited by 68 publications

References 131 publications

Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood–brain barrier

Differential permissivity of human cerebrovascular endothelial cells to enterovirus infection and specificities of serotype EV-A71 in crossing an in vitro model of the human blood–brain barrier

Evolution of Poliovirus Defective Interfering Particles Expressing Gaussia Luciferase

Infection of human islets of langerhans with two strains of coxsackie B virus serotype 1: Assessment of virus replication, degree of cell death and induction of genes involved in the innate immunity pathway

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