An ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion protein

Butler-Cole, C.; Wagner, Mary J.; Silva, Melissa Da; Brown, Gordon D.; Burke, Robert D.; Upton, Chris

doi:10.1186/1743-422x-4-76

Cited by 13 publications

(13 citation statements)

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“…Deletions seem to be an additional or alternative mechanism to generate profilin isovariants with differential physicochemical properties, e.g. the human PROF III and a virus profilin homologue [47] . We have shown in this work the presence of deletions in 47 sequences of profilin, which also exhibit differential properties (MW, pI, post-translational modification sites), supporting the existence of this mechanism to generate profilin variability.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Profilin Polymorphism in Pollen with a Focus on Multifunctionality

et al. 2012

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Profilin, a multigene family involved in actin dynamics, is a multiple partners-interacting protein, as regard of the presence of at least of three binding domains encompassing actin, phosphoinositide lipids, and poly-L-proline interacting patches. In addition, pollen profilins are important allergens in several species like Olea europaea L. (Ole e 2), Betula pendula (Bet v 2), Phleum pratense (Phl p 12), Zea mays (Zea m 12) and Corylus avellana (Cor a 2). In spite of the biological and clinical importance of these molecules, variability in pollen profilin sequences has been poorly pointed out up until now. In this work, a relatively high number of pollen profilin sequences have been cloned, with the aim of carrying out an extensive characterization of their polymorphism among 24 olive cultivars and the above mentioned plant species. Our results indicate a high level of variability in the sequences analyzed. Quantitative intra-specific/varietal polymorphism was higher in comparison to inter-specific/cultivars comparisons. Multi-optional posttranslational modifications, e.g. phosphorylation sites, physicochemical properties, and partners-interacting functional residues have been shown to be affected by profilin polymorphism. As a result of this variability, profilins yielded a clear taxonomic separation between the five plant species. Profilin family multifunctionality might be inferred by natural variation through profilin isovariants generated among olive germplasm, as a result of polymorphism. The high variability might result in both differential profilin properties and differences in the regulation of the interaction with natural partners, affecting the mechanisms underlying the transmission of signals throughout signaling pathways in response to different stress environments. Moreover, elucidating the effect of profilin polymorphism in adaptive responses like actin dynamics, and cellular behavior, represents an exciting research goal for the future.

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Section: Discussionmentioning

confidence: 99%

Characterization of Profilin Polymorphism in Pollen with a Focus on Multifunctionality

et al. 2012

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“…Our knowledge about the pathogenesis of mousepox, genetic resistance to disease, and mechanisms responsible for induction of the protective immune response is well defined. However, the understanding of the cell biology of ECTV infection is surprisingly low, despite many publications investigating ECTV infection at the cellular level [Butler‐Cole et al, ; Wilton et al, ; Erez et al, ]. Therefore, VACV still excels in studies investigating biological and molecular mechanisms of virus–host cell interactions.…”

Section: Introductionmentioning

confidence: 99%

Remodeling of the fibroblast cytoskeletal architecture during the replication cycle of Ectromelia virus: A morphological in vitro study in a murine cell line

et al. 2016

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Ectromelia virus (ECTV, the causative agent of mousepox), which represents the same genus as variola virus (VARV, the agent responsible for smallpox in humans), has served for years as a model virus for studying mechanisms of poxvirus-induced disease. Despite increasing knowledge on the interaction between ECTV and its natural host-the mouse-surprisingly, still little is known about the cell biology of ECTV infection. Because pathogen interaction with the cytoskeleton is still a growing area of research in the virus-host cell interplay, the aim of the present study was to evaluate the consequences of ECTV infection on the cytoskeleton in a murine fibroblast cell line. The viral effect on the cytoskeleton was reflected by changes in migration of the cells and rearrangement of the architecture of tubulin, vimentin, and actin filaments. The virus-induced cytoskeletal rearrangements observed in these studies contributed to the efficient cell-to-cell spread of infection, which is an important feature of ECTV virulence. Additionally, during later stages of infection L929 cells produced two main types of actin-based cellular protrusions: short (actin tails and "dendrites") and long (cytoplasmic corridors). Due to diversity of filopodial extensions induced by the virus, we suggest that ECTV represents a valuable new model for studying processes and pathways that regulate the formation of cytoskeleton-based cellular structures. © 2016 Wiley Periodicals, Inc.

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“…There is a wealth of knowledge on the pathogenesis of ECTV and the murine immune response to infection. Despite this, there is surprisingly little known regarding the cell biology of infection, with research so far delving into such areas as viral subversion of the immune system (42,66,67), the ubiquitin proteasome system (34,78), viral-mediated syncytium formation (22), and preliminary studies on intracellular transport and intercellular spread (2,4). The high level of conservation between VACV and ECTV genomes affords the opportunity to address the contribution of subcellular transport pathways to virulence in a natural host (8).…”

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confidence: 99%

Loss of Cytoskeletal Transport during Egress Critically Attenuates Ectromelia Virus Infection In Vivo

Lynn

Horsington

Ter

et al. 2012

J Virol

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d Egress of wrapped virus (WV) to the cell periphery following vaccinia virus (VACV) replication is dependent on interactionswith the microtubule motor complex kinesin-1 and is mediated by the viral envelope protein A36. Here we report that ectromelia virus (ECTV), a related orthopoxvirus and the causative agent of mousepox, encodes an A36 homologue (ECTV-Mos-142) that is highly conserved despite a large truncation at the C terminus. Deleting the ECTV A36R gene leads to a reduction in the number of extracellular viruses formed and to a reduced plaque size, consistent with a role in microtubule transport. We also observed a complete loss of virus-associated actin comets, another phenotype dependent on A36 expression during VACV infection. ECTV ⌬A36R was severely attenuated when used to infect the normally susceptible BALB/c mouse strain. ECTV ⌬A36R replication and spread from the draining lymph nodes to the liver and spleen were significantly reduced in BALB/c mice and in Rag-1-deficient mice, which lack T and B lymphocytes. The dramatic reduction in ECTV ⌬A36R titers early during the course of infection was not associated with an augmented immune response. Taken together, these findings demonstrate the critical role that subcellular transport pathways play not only in orthopoxvirus infection in an in vitro context but also during orthopoxvirus pathogenesis in a natural host. Furthermore, despite the attenuation of the mutant virus, we found that infection nonetheless induced protective immunity in mice, suggesting that orthopoxvirus vectors with A36 deletions may be considered another safe vaccine alternative.T he crowded, densely packed cytoplasm presents a significant hurdle to the subcellular transport of viruses, both in the translocation of viruses to their site of replication following cell entry and in the subsequent egress of progeny viruses to the cell periphery (16,18,29,69,70). This hurdle is most acute for large double-stranded DNA (dsDNA) viruses such as those belonging to the orthopoxvirus genus, which includes variola virus (VARV) and ectromelia virus (ECTV), the causative agents of smallpox and mousepox, respectively, and the prototypical orthopoxvirus, vaccinia virus (VACV). These viruses have a complicated replication cycle that has been studied best at the cellular level with VACV. Vaccinia virus replication produces two infectious forms: mature intracellular virus (MV), which has a single membrane and is generated at the so-called virus factory; and wrapped virus (WV), which is derived from MV and acquires an additional double membrane at the trans-Golgi network or early endosome compartment (33, 58). While it is apparent that microtubule transport plays a critical role at multiple stages during VACV replication, the stage best characterized at the molecular level is the transport of WV from the trans-Golgi network to the cell periphery (27,32,57,75,76). Once there, WV fuse with the plasma membrane and are released either directly or following the transient activation of actin-based motility ...

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An ectromelia virus profilin homolog interacts with cellular tropomyosin and viral A-type inclusion protein

Cited by 13 publications

References 44 publications

Characterization of Profilin Polymorphism in Pollen with a Focus on Multifunctionality

Characterization of Profilin Polymorphism in Pollen with a Focus on Multifunctionality

Remodeling of the fibroblast cytoskeletal architecture during the replication cycle of Ectromelia virus: A morphological in vitro study in a murine cell line

Loss of Cytoskeletal Transport during Egress Critically Attenuates Ectromelia Virus Infection In Vivo

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