Differential Requirements for COPI Coats in Formation of Replication Complexes among Three Genera of
            <i>Picornaviridae</i>

Gazina, Elena V.; Mackenzie, Jason M.; Gorrell, Rebecca J.; Anderson, David

doi:10.1128/jvi.76.21.11113-11122.2002

Cited by 97 publications

(139 citation statements)

References 54 publications

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“…The authors found that viral vesicles bud from the ER but do not fuse with the ER/ Golgi intermediate complex and suggested that the cellular COPII machinery participates in the induction of vesicles suitable for poliovirus replication. However, the inhibition of poliovirus and rhinovirus RNA replication by brefeldin A directly contradicts this hypothesis (20,30). Brefeldin A inhibits formation of COPI but not COPII vesicles.…”

Section: Discussionmentioning

confidence: 77%

“…The mechanisms of vesicle production and replication complex formation in picornavirus-infected cells have not been defined. The vesicles, which are induced by the synthesis of 2BC, 2C, and 3A proteins, may initially form as COPII vesicles (57), autophagic vesicles (59,61), or COPI vesicles (30). Regardless of the origin of picornavirus-induced vesicles, some viral proteins must interact with host cell proteins to generate the membrane alterations that occur in the cell and lead to the formation of replication complexes.…”

mentioning

confidence: 99%

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Amino Acid Changes in Proteins 2B and 3A Mediate Rhinovirus Type 39 Growth in Mouse Cells

Harris

Racaniello

2005

J Virol

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Many steps of viral replication are dependent on the interaction of viral proteins with host cell components. To identify rhinovirus proteins involved in such interactions, human rhinovirus 39 (HRV39), a virus unable to replicate in mouse cells, was adapted to efficient growth in mouse cells producing the viral receptor ICAM-1 (ICAM-L cells). Amino acid changes were identified in the 2B and 3A proteins of the adapted virus, RV39/L. Changes in 2B were sufficient to permit viral growth in mouse cells; however, changes in both 2B and 3A were required for maximal viral RNA synthesis in mouse cells. Examination of infected HeLa cells by electron microscopy demonstrated that human rhinoviruses induced the formation of cytoplasmic membranous vesicles, similar to those observed in cells infected with other picornaviruses. Vesicles were also observed in the cytoplasm of HRV39-infected mouse cells despite the absence of viral RNA replication. Synthesis of picornaviral nonstructural proteins 2C, 2BC, and 3A is known to be required for formation of membranous vesicles. We suggest that productive HRV39 infection is blocked in ICAM-L cells at a step posttranslation and prior to the formation of a functional replication complex. The observation that changes in HRV39 2B and 3A proteins lead to viral growth in mouse cells suggests that one or both of these proteins interact with host cell proteins to promote viral replication.Picornaviruses are small RNA viruses with a single-stranded, positive-sense genome of approximately 7 to 8 kb enclosed in a nonenveloped, icosahedral capsid. These viruses are responsible for a wide range of diseases including foot-and-mouth disease, hepatitis, poliomyelitis, and the common cold. Following cell entry, the viral genome is translated as a single polyprotein that is co-and posttranslationally cleaved by viral proteases, yielding both precursor proteins and end products. Many of the precursor proteins are essential for virus replication, with functions distinct from the end products (29,40,42). Four structural proteins produced from the P1 region of the genome form the viral capsid. Nonstructural proteins of the P2 and P3 region of the genome encode all of the viral proteins responsible for genomic RNA replication.Viral genome replication occurs on the surface of cytoplasmic vesicles induced by the synthesis of viral proteins 2C and 3A and the precursor 2BC (70). These vesicles are formed in conjunction with massive cell membrane proliferation (4, 7) and increased cellular synthesis of phospholipids (32). With the exception of the two viral proteases 2A pro and 3C pro , all of the nonstructural proteins have been found on the surface of these vesicles and are thought to interact in the replication complex (26,59,61,70). The vesicles assemble into a rosette, and the replication complex forms on the inner face of the rosette (13, 26). Salt-induced dissociation of the rosette demonstrated that the individual vesicles themselves can also support replication initiation and elongation (26). Neither t...

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Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

Amino Acid Changes in Proteins 2B and 3A Mediate Rhinovirus Type 39 Growth in Mouse Cells

Harris

Racaniello

2005

J Virol

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“…In addition, we tested whether mengovirus, a member of the cardiovirus genus known to be resistant to BFA (7,9), is sensitive to treatment with GCA. BGM cells (CVB3/ EV71), HeLa cells (CVA21), and BHK-21 cells (mengovirus) were infected with the different viruses and incubated in the presence or absence of GCA.…”

Section: Vol 84 2010 Effects Of Gbf1 Inhibitors On Enterovirus Replmentioning

confidence: 99%

Differential Effects of the Putative GBF1 Inhibitors Golgicide A and AG1478 on Enterovirus Replication

Linden

Schaar

Lanke

et al. 2010

J Virol

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The genus Enterovirus, belonging to the family Picornaviridae, includes well-known pathogens, such as poliovirus, coxsackievirus, and rhinovirus. Brefeldin A (BFA) impedes replication of several enteroviruses through inhibition of Golgi-specific BFA resistance factor 1 (GBF1), a regulator of secretory pathway integrity and transport. GBF1 mediates the GTP exchange of Arf1, which in activated form recruits coatomer protein complex I (COP-I) to Golgi vesicles, a process important in transport between the endoplasmic reticulum and Golgi vesicles. Recently, the drugs AG1478 and Golgicide A (GCA) were put forward as new inhibitors of GBF1. In this study, we investigated the effects of these putative GBF1 inhibitors on secretory pathway function and enterovirus replication. We show that both drugs induced fragmentation of the Golgi vesicles and caused dissociation of Arf1 and COP-I from Golgi membranes, yet they differed in their effect on GBF1 localization. The effects of AG1478, but not those of GCA, could be countered by overexpression of Arf1, indicating a difference in their molecular mechanism of action. Consistent with this idea, we observed that GCA drastically reduced replication of coxsackievirus B3 (CVB3) and other human enterovirus species, whereas AG1478 had no effect at all on enterovirus replication. Time-of-addition studies and analysis of RNA replication using a subgenomic replicon both showed that GCA suppresses RNA replication of CVB3, which could be countered by overexpression of GBF1. These results indicate that, in contrast to AG1478, GCA inhibits CVB3 RNA replication by targeting GBF1. AG1478 and GCA may be valuable tools to further dissect enterovirus replication.

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“…Another possibility is that tyrosine 78 could be involved in crosstalking to cellular host factors that are essential for virus assembly. Several host proteins such as COPI and COPII factors have been reported to be involved in poliovirus production and formation of replication complexes in picornavirus (Rust et al, 2001;Gazina et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Tyrosine 78 of premembrane protein is essential for assembly of West Nile virus

Tan

Bhuvanakantham

et al. 2009

Journal of General Virology

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Flavivirus premembrane (prM) protein plays an important role in conformational folding of the envelope (E) protein and protects it against premature fusion in acidic vesicles of the Golgi network. Currently, molecular determinants on the prM protein ectodomain which mediate critical steps during the flavivirus assembly process are poorly characterized. In this study, bioinformatics analysis and alanine scanning mutagenesis showed that the amino acid triplet valine 76, tyrosine 78 and glycine 79 is absolutely conserved among flavivirus prM ectodomains. Triple mutations engineered at these residues in prM ectodomain of West Nile virus (WNV) completely abrogated virus infectivity. Site-directed mutagenesis of prM protein revealed that tyrosine 78 of the amino acid triplet was required for virus infectivity and secretion. The mutation did not affect folding, post-translational modifications and trafficking of the prM and E proteins. Ultrastructural studies using transmission electron microscopy confirmed that virus particle formation was blocked by tyrosine 78 mutation. Specificity of assembly defect conferred by tyrosine 78 mutation was demonstrated by positive and negative trans complementation studies. Collectively, these results defined tyrosine 78 as a novel critical determinant present on prM protein ectodomain that is required for flavivirus assembly. Molecular dissection of prM protein function provides the crucial knowledge much needed in the elucidation of flavivirus particle formation.

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Differential Requirements for COPI Coats in Formation of Replication Complexes among Three Genera of Picornaviridae

Cited by 97 publications

References 54 publications

Amino Acid Changes in Proteins 2B and 3A Mediate Rhinovirus Type 39 Growth in Mouse Cells

Amino Acid Changes in Proteins 2B and 3A Mediate Rhinovirus Type 39 Growth in Mouse Cells

Differential Effects of the Putative GBF1 Inhibitors Golgicide A and AG1478 on Enterovirus Replication

Tyrosine 78 of premembrane protein is essential for assembly of West Nile virus

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