Interactions between human endogenous and exogenous retroviruses

Retrovirus genes have become inserted into the human genome for more than one million years. These retroviruses are now inactivated due to mutation, such as deletions or nonsense mutations. After mutation, retroviruses eventually become fixed in the genome in the endogenous form and exist as traces of ancient viruses. These retroviruses are called human endogenous retroviruses (HERVs). HERVs cannot make fully active viruses, but a number of viral proteins (or even virus particles) are expressed under various conditions. By comparison with ERVs, some exogenous retroviruses are still infectious and cause serious diseases threatening human life. Recent studies have shown that some elements of HERVs are closely related to other exogenous retroviruses, including human immunodeficiency virus (HIV). This review will describe the regulation and interaction between HERVs and other active viral infections. In addition, we introduce the development of vaccines and therapeutic agents against these viral infections through the use of HERV elements.     

Interactions of mitochondria with the actin cytoskeleton

Interactions between mitochondria and the cytoskeleton are essential for normal mitochondrial morphology, motility and distribution. While microtubules and their motors have been established as important factors for mitochondrial transport, emerging evidence indicates that mitochondria interact with the actin cytoskeleton in many cell types. In certain fungi, such as the budding yeast and Aspergillus, or in plant cells mitochondrial motility is largely actin-based. Even in systems such as neurons, where microtubules are the primary means of long-distance mitochondrial transport, the actin cytoskeleton is required for short-distance mitochondrial movements and for immobilization of the organelle at the cell cortex. The actin cytoskeleton is also involved in the immobilization of mitochondria at the cortex in cultured tobacco cells and in budding yeast. While the exact nature of these immobilizations is not known, they may be important for retaining mitochondria at sites of high ATP utilization or at other cellular locations where they are needed. Recent findings also indicate that mutations in actin or actin-binding proteins can influence mitochondrial pathways leading to cell death. Thus, mitochondria-actin interactions contribute to apoptosis.     

Direct modulation of the host cell cytoskeleton by Salmonella actin-binding proteins

Invasive Salmonella trigger their own uptake into non-phagocytic eukaryotic cells by delivering virulence proteins that stimulate signaling pathways and remodel the actin cytoskeleton. It has recently emerged that Salmonella encodes two actin-binding proteins, SipC and SipA, which together efficiently nucleate actin polymerization and stabilize the resulting supramolecular filament architecture. Therefore, Salmonella might directly initiate actin polymerization independently of the cellular Arp2/3 complex early in the cell entry process. This is an unprecedented example of a direct intervention strategy to facilitate entry of a pathogen into a target cell. Here, we discuss the Salmonella actin-binding proteins and how they might function in combination with entry effectors that stimulate Rho GTPases. We propose that membrane-targeted bacterial effector proteins might trigger actin polymerization through diverse mechanisms during cell entry by bacterial pathogens.     

Progressive reorganization of the host cell cytoskeleton during adenovirus infection.

Infection of cells with adenovirus lead to a characteristic reorganization of all cytoskeleton systems, starting with alterations at the microtubuli of the cells. During this progress, the flat, extended, and polar morphology of the cytoskeleton became nonpolar and rounder. These rearrangements were initiated before the appearance of adenovirus structural proteins hexon and fiber, as well as before the shutoff of host protein synthesis. We conclude that these alterations reflect a specific reorganization rather than an unorganized breakdown of the cell during adenovirus infection.     

Perturbation and exploitation of host cell cytoskeleton by periodontal pathogens

Some periodontal pathogens disrupt epithelial barriers and cellular adhesion to the extracellular matrix, which affects the cytoskeleton. Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans exploit the cytoskeleton during their uptake by epithelial cells. Treponema denticola perturbs actin and actin-regulating pathways in host cells. Cytoskeletal dysfunction due to pathogenic bacteria may impair physiologic remodeling and wound repair in the periodontium.     

Interactions between exogenous and endogenous retroviruses

Retroviruses are distinguished from other viruses by several features. Notably, some retroviruses are present as normal elements in the genomes of virtually all vertebrates (endogenous proviruses). Others are exogenous, i.e. horizontally transmitted agents, many of which cause fatal diseases. The endogenous retroviruses are genetically transmitted and to a large extent their significance is uncertain. However, there is evidence suggesting that they contribute to the development of diseases in several animal species. Most importantly, some endogenous retroviruses are capable of interacting with exogenous counterparts through a variety of different mechanisms with serious consequences to the host. Conversely, others are advantageous in that they protect against exogenous retroviruses. In this review various types of interactions between endogenous and exogenous retroviruses are discussed, including receptor interference, recombination, phenotypic mixing, immunological interactions and heterologoustrans-activation.     

Interactions between laminin receptor and the cytoskeleton during translation and cell motility

Human laminin receptor acts as both a component of the 40S ribosomal subunit to mediate cellular translation and as a cell surface receptor that interacts with components of the extracellular matrix. Due to its role as the cell surface receptor for several viruses and its overexpression in several types of cancer, laminin receptor is a pathologically significant protein. Previous studies have determined that ribosomes are associated with components of the cytoskeleton, however the specific ribosomal component(s) responsible has not been determined. Our studies show that laminin receptor binds directly to tubulin. Through the use of siRNA and cytoskeletal inhibitors we demonstrate that laminin receptor acts as a tethering protein, holding the ribosome to tubulin, which is integral to cellular translation. Our studies also show that laminin receptor is capable of binding directly to actin. Through the use of siRNA and cytoskeletal inhibitors we have shown that this laminin receptor-actin interaction is critical for cell migration. These data indicate that interactions between laminin receptor and the cytoskeleton are vital in mediating two processes that are intimately linked to cancer, cellular translation and migration.     

Interactions between Bdellovibrio and its host cell.

The bdellovibrios are extremely small bacteria with the unique property of being parasites of other (gram-negative) bacteria. In the presence of viable and susceptible bacteria a Bdellovibrio cell physically 'attacks' an individual host cell, attaches to its surface, penetrates the cell wall, and multiples within the periplasmic (intramural) space of its prey. The invading Bdellovibrio and its progeny degrade and consume the cellular constituents of the invaded host bacterium. This process finally results in complete lysis of the host cell and release of the Bdellovibrio progeny. From a population of parasitic bdellovibrios, derivatives can be selected that grow on complex nutrient media. Currently, none of the different nutritional types can be propagated in a fully defined synthetic medium. By degradation of the cellular constituents of the host the Bdellovibrio cell in its periplasmic space has available all the monomeric subunits needed to synthesis of the macromolecules. Peculiarities of Bdellovibrio metabolism with respect to uptake of preformed molecules and energy efficiency are discussed.     

Poisons, ruffles and rockets: bacterial pathogens and the host cell cytoskeleton

The cytoskeleton of eukaryotic cells is affected by a number of bacterial and viral pathogens. In this review we consider three recurring themes of cytoskeletal involvement in bacterial pathogenesis: 1) the effect of bacterial toxins on actin-regulating small GTP-binding proteins; 2) the invasion of non-phagocytic cells by the bacterial induction of ruffles at the plasma membrane; 3) the formation of actin tails and pedestals by intracellular and extracellular bacteria, respectively. Considerable progress has been made recently in the characterization of these processes. It is becoming clear that bacterial pathogens have developed a variety of sophisticated mechanisms for utilizing the complex cytoskeletal system of host cells. These bacterially-induced processes are now providing unique insights into the regulation of fundamental eukaryotic mechanisms.     

The effect of Chlamydia trachomatis infection on the host cell cytoskeleton and membrane compartments

Human epithelial cells and the McCoy cell line were infected with Chlamydia trachomatis, serotype E. The organization of the cytoplasm was then studied with probes which stained cytoskeletal components and membrane compartments. The major actin-containing stress fibre bundles were not associated with inclusions due to the peri-basal and peri-apical location of these bundles within the host cell. The cytokeratin network was distorted by the presence of inclusions so that a common basket of these intermediate filaments surrounded both nucleus and peri-nuclear inclusions. The microtubule network was similarly distorted, but the nucleus and inclusion were surrounded by separate rather than joint baskets of tubules. After reversible depolymerization by nocadazole the microtubules in amniotic epithelial cells began to reassemble at the peri-nuclear microtubule-organizing centre, so that independent microtubule networks were rapidly regenerated around the nucleus and inclusion. Mitochondria of amniotic epithelial cells were vitally stained with the fluorescent probe DiOC6 (3,3'-dihexyloxacarbocyanine iodide) after 48 h of infection and found to be widely distributed throughout the host cytoplasm. When the morphology of the Golgi complex was examined with C6-NBD-ceramide (N-[7-(4-nitrobenzo-2-oxa-1,3-diazole)] aminocaproyl sphingosine) the main cisternae were retained in a juxta-nuclear position, although scattered stained structures were also present close to the cytoplasmic surface of the inclusion. These results demonstrate that the peri-nuclear position of inclusions is determined by the configuration of the cytoskeleton, and that normal host-cell architecture is maintained during infection, albeit in a distorted form.     

Submembraneous microtubule cytoskeleton: interaction of TRPP2 with the cell cytoskeleton

TRPP2, also called polycystin-2, the gene product of PKD2, is a membrane protein defective in 10-15% of cases of autosomal dominant polycystic kidney disease. Mutations in PKD2 are also associated with extrarenal disorders, such as hepatic cystogenesis and cardiovascular abnormalities. TRPP2 is a Ca-permeable nonselective cation channel present in the endoplasmic reticulum and plasma membrane, as well as in cilia of renal epithelial and embryonic nodal cells, in which it likely forms part of a flow sensor. Recent studies have identified a number of TRPP2-interacting proteins, of which many are cytoskeletal components. Work from our and other laboratories indicates that cytoskeletal partner proteins seem to play important, albeit highly complex, roles in the regulation of TRPP2 expression, localization and channel function. This minireview covers current knowledge about cytoskeletal interactions with TRPP2, and suggests that mutations in proteins of the TRPP2-cytoskeleton complex may be implicated in the pathogenesis of autosomal dominant polycystic kidney disease.     

Microtubule cytoskeleton behavior in the initial steps of host cell invasion by Besnoitia besnoiti

Besnoitia besnoiti is a protozoan parasite responsible for bovine besnoitiosis. Indirect immunofluorescence showed that isolated B. besnoiti possesses a set of subpellicular microtubules, radiating from the apical end and extending for more than 2/3 of the cell body. Upon interaction with the host cell, B. besnoiti undergoes dramatic modifications of shape and surface, as revealed by atomic force microscopy, accompanied by a distinct tubulin labeling on the posterior region. In the host cell, the microtubule cytoskeleton shows a re-arrangement around the invading parasite suggesting a filamentous interaction with the parasite cytoskeleton during invasion.     

Interactions of the human red cell membrane tyrosine kinase with heparin

Heparin interacts with protein kinases in various ways; the different patterns of behavior of heparin towards protein kinases contributes to the characterization of these enzymes. We studied the interactions between heparin and a new type of tyrosine kinase extracted from the normal human red cell membrane. We found that heparin inhibited kinase activity by competition with ATP. Furthermore the interaction of heparin with the red cell membrane tyrosine kinase allowed us to use heparin-agarose chromatography as a step towards tyrosine kinase purification.     

Interactions of pathogenic mycobacteria with host macrophages

Tuberculosis, caused by the bacterium Mycobacterium tuberculosis, is one of the most deadly infectious diseases across the globe. The success of M. tuberculosis is related to its capacity to survive and replicate in macrophages, cells of the host innate immune system that are designed to detect and eliminate pathogens [1,2]. In this review, we will focus on the mechanisms used by the innate system of the host to detect and eliminate mycobacteria and the strategies used by M. tuberculosis to overcome host responses to establish a successful infection.     

MicroRNAs and human retroviruses

MicroRNAs (miRNAs) are small non-coding RNAs that control a multitude of critical processes in mammalian cells. Increasing evidence has emerged that host miRNAs serve in animal cells to restrict viral infections. In turn, many viruses encode RNA silencing suppressors (RSS) which are employed to moderate the potency of the cell's miRNA selection against viral replication. Some viruses also encode viral miRNAs. In this review, we summarize findings from human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type 1 (HTLV-1) that illustrate examples of host cell miRNAs that target the viruses, of RSS encoded by viruses, and of host cell miRNA profile changes that are seen in infected cells. This article is part of a Special Issue entitled: MicroRNAs in viral gene regulation.