scholarly journals Infection with Replication-deficient Adenovirus Induces Changes in the Dynamic Instability of Host Cell Microtubules

2006 ◽  
Vol 17 (8) ◽  
pp. 3557-3568 ◽  
Author(s):  
James C. Warren ◽  
Adam Rutkowski ◽  
Lynne Cassimeris
Keyword(s):  
Host Cell ◽  
Dynamic Instability ◽  
Infection Process ◽  
Microtubule Dynamics ◽  
Cell Periphery ◽  
Adenovirus Infection ◽  
Drug Induced ◽  
Infected Cells ◽  
The Stability ◽  
Induced Changes

Adenovirus translocation to the nucleus occurs through a well characterized minus end-directed transport along microtubules. Here, we show that the adenovirus infection process has a significant impact on the stability and dynamic behavior of host cell microtubules. Adenovirus-infected cells had elevated levels of acetylated and detyrosinated microtubules compared with uninfected cells. The accumulation of modified microtubules within adenovirus-infected cells required active RhoA. Adenovirus-induced changes in microtubule dynamics were characterized at the centrosome and at the cell periphery in living cells. Adenovirus infection resulted in a transient enhancement of centrosomal microtubule nucleation frequency. At the periphery of adenovirus-infected cells, the dynamic instability of microtubules plus ends shifted toward net growth, compared with the nearly balanced growth and shortening observed in uninfected cells. In infected cells, microtubules spent more time in growth, less time in shortening, and underwent catastrophes less frequently compared with those in uninfected cells. Drug-induced inhibition of Rac1 prevented most of these virus-induced shifts in microtubule dynamic instability. These results demonstrate that adenovirus infection induces a significant stabilizing effect on host cell microtubule dynamics, which involve, but are not limited to, the activation of the RhoGTPases RhoA and Rac1.

scholarly journals Use of a fluorescent probe to assess the activities of candidate agents against intracellular forms of Encephalitozoon microsporidia.

1997 ◽  
Vol 41 (2) ◽  
pp. 337-344 ◽  
Author(s):  
G J Leitch ◽  
M Scanlon ◽  
A Shaw ◽  
G S Visvesvara ◽  
S Wallace
Keyword(s):  
Host Cell ◽  
Fluorescent Probe ◽  
Cultured Cells ◽  
Morphological Changes ◽  
Parasitophorous Vacuole ◽  
Detectable Effect ◽  
Drug Induced ◽  
Encephalitozoon Intestinalis ◽  
Infected Cells

Microsporidia are obligate intracellular protozoan parasites. Three species of the genus Encephalitozoon are among the microsporidia that infect immunodeficient humans. These species, Encephalitozoon cuniculi, Encephalitozoon hellem, and Encephalitozoon intestinalis, all develop in a parasitophorous vacuole within a host cell. The present study describes a method that uses the fluorescent probe calcein and confocal microscopy to detect drug-induced effects in Encephalitozoon-infected green monkey kidney cells. The effects were as follows: (i) changes in parasite organization within the parasitophorous vacuole; (ii) swelling and gross morphological changes of parasite developing stages in situ; (iii) killing of developing parasite stages in situ, detected by their uptake of the fluorescent probe; and (iv) reduction in the viability of the host cell population, assessed by the loss of the probe. Verapamil and itraconazole were used to increase the vital dye loading by both uninfected and infected cells. Agents with known antimicrosporidial activity, albendazole and fumagillin, caused all three types of parasite changes at concentrations that had no detectable effect on host cell viability. The effective doses of albendazole and fumagillin that caused swelling and disorganization of parasite developing stages were 5 x 10(-7) and 10(-6) M respectively. Killing of developing stages was detected at 10-fold-higher concentrations for these agents and at 10(-5) M for metronidazole. This method can be used to screen candidate antimicrosporidial agents in infected cultured cells.

scholarly journals The microtubule lattice and plus-end association of Drosophila Mini spindles is spatially regulated to fine-tune microtubule dynamics

2011 ◽  
Vol 22 (22) ◽  
pp. 4343-4361 ◽  
Author(s):  
Joshua D. Currie ◽  
Shannon Stewman ◽  
Gregory Schimizzi ◽  
Kevin C. Slep ◽  
Ao Ma ◽  
...  
Keyword(s):  
Dynamic Instability ◽  
Function Analysis ◽  
Microtubule Dynamics ◽  
Cell Periphery ◽  
Cell Interior ◽  
Microtubule Associated Proteins ◽  
Contact Sites ◽  
Associated Proteins ◽  
Fine Tune

Individual microtubules (MTs) exhibit dynamic instability, a behavior in which they cycle between phases of growth and shrinkage while the total amount of MT polymer remains constant. Dynamic instability is promoted by the conserved XMAP215/Dis1 family of microtubule-associated proteins (MAPs). In this study, we conducted an in vivo structure–function analysis of the Drosophila homologue Mini spindles (Msps). Msps exhibits EB1-dependent and spatially regulated MT localization, targeting to microtubule plus ends in the cell interior and decorating the lattice of growing and shrinking microtubules in the cell periphery. RNA interference rescue experiments revealed that the NH2-terminal four TOG domains of Msps function as paired units and were sufficient to promote microtubule dynamics and EB1 comet formation. We also identified TOG5 and novel inter-TOG linker motifs that are required for targeting Msps to the microtubule lattice. These novel microtubule contact sites are necessary for the interplay between the conserved TOG domains and inter-TOG MT binding that underlies the ability of Msps to promote MT dynamic instability.

scholarly journals The Salmonella effector SifA initiates a kinesin-1 and kinesin-3 recruitment process mirroring that mediated by Arl8a/b

2021 ◽  
Author(s):  
Ziyan Fang ◽  
Mathieu Fallet ◽  
Tomas Moest ◽  
Jean-Pierre Gorvel ◽  
Stéphane Méresse
Keyword(s):  
Host Cell ◽  
Molecular Motors ◽  
Molecular Motor ◽  
Host Protein ◽  
Recruitment Process ◽  
Membrane Compartment ◽  
Infected Cells ◽  
The Stability ◽  
Bacterial Effectors

When intracellular, pathogenic Salmonella reside in a membrane compartment composed of interconnected vacuoles and tubules, the formation of which depends on the translocation of bacterial effectors into the host cell. Cytoskeletons and their molecular motors are prime targets for these effectors. In this study, we show that the microtubule molecular motor KIF1Bß, a member of the kinesin-3 family, is a key element for the establishment of the Salmonella replication niche as its absence is detrimental to the stability of bacterial vacuoles and the formation of associated tubules. Kinesin-3 interacts with the Salmonella effector SifA but also with SKIP, a host protein complexed to SifA. The interaction with SifA is essential for the recruitment of kinesin-3 on Salmonella vacuoles while that with SKIP is incidental. In the non-infectious context, however, the interaction with SKIP is essential for the recruitment and activity of kinesin-3 on a part of lysosomes. Finally, our results show that in infected cells, the presence of SifA establishes a kinesin-1 and kinesin-3 recruitment pathway that is analogous to and functions independently of that mediated by the Arl8a/b GTPases.

DRUG-INDUCED CHANGES IN THE CYTOPLASMIC RIBONUCLEOPROTEIN CONSTITUENTS OF BRAIN TISSUE

1965 ◽  
Vol 43 (7) ◽  
pp. 959-975 ◽  
Author(s):  
J. J. Ghosh ◽  
R. K. Datta ◽  
K. C. Bhattacharyya
Keyword(s):  
Secondary Structure ◽  
Brain Tissue ◽  
Ribosomal Rna ◽  
Brain Cortex ◽  
Macromolecular Structure ◽  
Drug Induced ◽  
Brain Cortex Slices ◽  
Cortex Slices ◽  
The Stability ◽  
Induced Changes

Studies carried out on the properties of isolated ribosomes from drug-treated brain cortex slices indicate that ribosomes from drug-treated tissues are generally more susceptible to breakdown into smaller components such as proteins, nucleic acids, acid-soluble nucleotides, etc. It seems that some factor or factors responsible for the stability of the complex macromolecular structure of ribonucleoproteins of brain tissue are affected as a result of drug treatment. Ribosomal RNA from drug-treated brain tissue has been isolated under standardized conditions and the secondary structures of RNA have been studied by methods involving thermal hyperchromicity and reaction with formaldehyde. This latter study indicates that, during the action of some of these neuropharmacological drugs, the secondary structure of ribosomal RNA of brain tissue is partially lost. The loss in the stability of cytoplasmic ribonucleoproteins in drug-treated brain tissue may partly be due to the disorganization at the level of the secondary structure of the RNA component.

scholarly journals Ahead of the Curve: New Insights into Microtubule Dynamics

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 314 ◽  
Author(s):  
Ryoma Ohi ◽  
Marija Zanic
Keyword(s):  
Structural Biology ◽  
Dynamic Instability ◽  
Microtubule Dynamics ◽  
Cell Physiology ◽  
Gtp Hydrolysis ◽  
Key Features ◽  
To Come ◽  
Induced Changes ◽  
Tubulin Structure ◽  
Intense Research

Microtubule dynamics are fundamental for many aspects of cell physiology, but their mechanistic underpinnings remain unclear despite 40 years of intense research. In recent years, the continued union of reconstitution biochemistry, structural biology, and modeling has yielded important discoveries that deepen our understanding of microtubule dynamics. These studies, which we review here, underscore the importance of GTP hydrolysis-induced changes in tubulin structure as microtubules assemble, and highlight the fact that each aspect of microtubule behavior is the output of complex, multi-step processes. Although this body of work moves us closer to appreciating the key features of microtubule biochemistry that drive dynamic instability, the divide between our understanding of microtubules in isolation versus within the cellular milieu remains vast. Bridging this gap will serve as fertile grounds of cytoskeleton-focused research for many years to come.

Drug Induced Changes in Cell Organelles

1968 ◽  
Vol 26 ◽  
pp. 110-111
Author(s):  
Sarah A. Luse
Keyword(s):  
Clinical Medicine ◽  
Cell Organelles ◽  
Riboflavin Deficiency ◽  
Drug Induced ◽  
New Era ◽  
Health And Disease ◽  
In The Beginning ◽  
Cellular Pathology ◽  
Induced Changes ◽  
The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

COVID 19 – Eye Issues

2020 ◽  
Vol 5 (Special) ◽  
Keyword(s):  
Host Cell ◽  
Target Cell ◽  
Cell Receptor ◽  
Human Tissues ◽  
Type Ii ◽  
Cell Infection ◽  
Host Cell Receptor ◽  
Infected Cells ◽  
Cellular Entry

The coronavirus illness (COVID-19) is caused by a new recombinant SARS-CoV (SARS-CoV) virus (SARS-CoV-2). Target cell infection by SARS-CoV is mediated by the prickly protein of the coronavirus and host cell receptor, enzyme 2 converting angiotensin (ACE2) [3]. Similarly, a recent study suggests that cellular entry by SARS-CoV-2 is dependent on both ACE2 as well as type II transmembrane axial protease (TMPRSS2) [4]. This means that detection of ACE2 and PRSS2 expression in human tissues can predict potential infected cells and their respective effects in COVID-19 patients [1].

scholarly journals Host Cell Restriction Factors of Bunyaviruses and Viral Countermeasures

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 784
Author(s):  
Solène Lerolle ◽  
Natalia Freitas ◽  
François-Loïc Cosset ◽  
Vincent Legros
Keyword(s):  
Host Cell ◽  
Viral Entry ◽  
Current Knowledge ◽  
Restriction Factors ◽  
Antiviral State ◽  
Cellular Factors ◽  
Pathogenic Viruses ◽  
Genome Transcription ◽  
Infected Cells ◽  
Molecular Patterns

The Bunyavirales order comprises more than 500 viruses (generally defined as bunyaviruses) classified into 12 families. Some of these are highly pathogenic viruses infecting different hosts, including humans, mammals, reptiles, arthropods, birds, and/or plants. Host cell sensing of infection activates the innate immune system that aims at inhibiting viral replication and propagation. Upon recognition of pathogen-associated molecular patterns (PAMPs) by cellular pattern recognition receptors (PRRs), numerous signaling cascades are activated, leading to the production of interferons (IFNs). IFNs act in an autocrine and paracrine manner to establish an antiviral state by inducing the expression of hundreds of IFN-stimulated genes (ISGs). Some of these ISGs are known to restrict bunyavirus infection. Along with other constitutively expressed host cellular factors with antiviral activity, these proteins (hereafter referred to as “restriction factors”) target different steps of the viral cycle, including viral entry, genome transcription and replication, and virion egress. In reaction to this, bunyaviruses have developed strategies to circumvent this antiviral response, by avoiding cellular recognition of PAMPs, inhibiting IFN production or interfering with the IFN-mediated response. Herein, we review the current knowledge on host cellular factors that were shown to restrict infections by bunyaviruses. Moreover, we focus on the strategies developed by bunyaviruses in order to escape the antiviral state developed by the infected cells.

scholarly journals Revisiting Ehrlichia ruminantium Replication Cycle Using Proteomics: The Host and the Bacterium Perspectives

2021 ◽  
Vol 9 (6) ◽  
pp. 1144
Author(s):  
Isabel Marcelino ◽  
Philippe Holzmuller ◽  
Ana Coelho ◽  
Gabriel Mazzucchelli ◽  
Bernard Fernandez ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Host Cell ◽  
Cell Metabolism ◽  
Replication Cycle ◽  
Host Cells ◽  
Ehrlichia Ruminantium ◽  
Host Interaction ◽  
Infected Cells ◽  
Related Proteins

The Rickettsiales Ehrlichia ruminantium, the causal agent of the fatal tick-borne disease Heartwater, induces severe damage to the vascular endothelium in ruminants. Nevertheless, E. ruminantium-induced pathobiology remains largely unknown. Our work paves the way for understanding this phenomenon by using quantitative proteomic analyses (2D-DIGE-MS/MS, 1DE-nanoLC-MS/MS and biotin-nanoUPLC-MS/MS) of host bovine aorta endothelial cells (BAE) during the in vitro bacterium intracellular replication cycle. We detect 265 bacterial proteins (including virulence factors), at all time-points of the E. ruminantium replication cycle, highlighting a dynamic bacterium–host interaction. We show that E. ruminantium infection modulates the expression of 433 host proteins: 98 being over-expressed, 161 under-expressed, 140 detected only in infected BAE cells and 34 exclusively detected in non-infected cells. Cystoscape integrated data analysis shows that these proteins lead to major changes in host cell immune responses, host cell metabolism and vesicle trafficking, with a clear involvement of inflammation-related proteins in this process. Our findings led to the first model of E. ruminantium infection in host cells in vitro, and we highlight potential biomarkers of E. ruminantium infection in endothelial cells (such as ROCK1, TMEM16K, Albumin and PTPN1), which may be important to further combat Heartwater, namely by developing non-antibiotic-based strategies.

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