scholarly journals Host-dependent differences in replication strategy of the Sulfolobus Spindle-shaped Virus strain SSV9 (a.k.a., SSVK1): Lytic replication in hosts of the family Sulfolobaceae

2020 ◽  
Author(s):  
Ruben Michael Ceballos ◽  
Coyne Drummond ◽  
Carson Len Stacy ◽  
Elizabeth Padilla Crespo ◽  
Kenneth Stedman
Keyword(s):  
High Temperature ◽  
Virus Strain ◽  
Molecular Mechanisms ◽  
Transmission Rate ◽  
Lytic Replication ◽  
Host Interactions ◽  
Virion Release ◽  
The Family ◽  
Replication Strategy ◽  
Geographic Separation

ABSTRACTThe Sulfolobus Spindle-shaped Virus (SSV) system has become a model for studying thermophilic virus biology, including archaeal host-virus interactions and biogeography. Several factors make the SSV system amenable to studying archaeal genetic mechanisms (e.g., CRISPRs) as well as virus-host interactions in high temperature acidic environments. First, it has been shown that endemic populations of Sulfolobus, the reported SSV host, exhibit biogeographic structure. Second, the acidic (pH<4.5) high temperature (65-88°C) SSV habitats have low biodiversity, thus, diminishing opportunities for host switching. Third, SSVs and their hosts are readily cultured in liquid media and on gellan gum plates. Fourth, given the wide geographic separation between the various SSV-Sulfolobus habitats, the system is amenable for studying allopatric versus sympatric virus-host interactions. Previously, we reported that SSVs exhibit differential infectivity on allopatric and sympatric hosts. We also noticed a wide host range for virus strain SSV9 (a.k.a., SSVK1). For decades, SSVs have been described as “non-lytic” dsDNA viruses that infect species of the genus Sulfolobus and release virions via “blebbing” or “budding” as a preferred strategy over host lysis. Here, we show that SSVs infect more than one genus of the family Sulfolobaceae and, in allopatric hosts, SSV9 does not appear to release virions by blebbing. Instead, SSV9 appears to lyse all susceptible allopatric hosts tested, while exhibiting canonical non-lytic viral release via “blebbing” (historically reported for all other SSVs), on a single sympatric host. Lytic versus non-lytic virion release does not appear to be driven by multiplicity of infection (MOI). Greater relative stability of SSV9 compared to other SSVs (i.e., SSV1) in high temperature, low pH environments may contribute to higher transmission rates. However, neither higher transmission rate nor relative virulence in SSV9 infection drives replication profile (i.e., lytic versus non-lytic) in susceptible hosts. Although it is known that CRISPR-Cas systems offer protection against viral infection in prokaryotes, CRISPRS are not reported to be a determinant virus replication strategy. Thus, the genetic/molecular mechanisms underlying SSV9-induced lysis are unknown. These results suggest that there are unknown genetic elements, resulting from allopatric evolution, that drive virion release strategy in specific host strain-SSV strain pairings.

scholarly journals Host-dependent differences in replication and virion release strategy of the Sulfolobus Spindle-shaped Virus strain SSV9 (a.k.a., SSVK1): Lytic replication in hosts of the family Sulfolobaceae

2020 ◽  
Vol 2 (7A) ◽  
Author(s):  
Ruben Michael Ceballos ◽  
Carson Stacy ◽  
Coyne Drummond ◽  
Yeasin Ahmed ◽  
Samia Parveen ◽  
...  
Keyword(s):  
Extreme Environments ◽  
Lytic Replication ◽  
Broad Host Range ◽  
Host Interactions ◽  
Virion Release ◽  
The Family ◽  
Differential Infectivity ◽  
Host Lysis ◽  
Geographic Separation ◽  
Dsdna Viruses

The Sulfolobus Spindle-shaped Virus (SSV) system is a model for studying thermophilic archaeal virus biology. Several factors make the SSV system amenable to studying archaeal genetics and virus-host interactions in extreme environments. It has been shown that populations of Sulfolobus, the natural host, exhibit biogeographic structure. The acidic (pH<4.5) high temperature (65-88°C) habitats have low biodiversity, which diminishes prospects for host switch. SSVs and their hosts are readily cultured in liquid media and on plates. Given the wide geographic separation between various SSV-Sulfolobus habitats, the system is also amenable to studying allopatric versus sympatric virus-host interactions. We previously reported that SSVs exhibit differential infectivity on allopatric and sympatric hosts. We discovered a strikingly broad host-range for strain SSV9 (a.k.a., SSVK1). For decades, SSVs have been described as “non-lytic” dsDNA viruses that infect species of Sulfolobus and release virus particles via blebbing as a preferred strategy over host lysis (in reported laboratory infections). Here, we show, that SSVs infect more than one genus of the family Sulfolobaceae and, in allopatric hosts, SSV9 does not release virions via blebbing. Instead, SSV9 appears to lyse all susceptible allopatric hosts, while exhibiting canonical non-lytic virion release (historically reported for SSVs) on a single sympatric host. Lytic versus non-lytic virus release does not appear to be driven by multiplicity of infection. Data suggest that SSV9 is more stable than other SSVs in suspension; however, genetic substrates (e.g., CRISPR profiles) underlying non-lytic versus lytic virion release remain unresolved and are the subject of ongoing investigation.

scholarly journals Host-Dependent Differences in Replication Strategy of the Sulfolobus Spindle-Shaped Virus Strain SSV9 (a.k.a., SSVK1): Infection Profiles in Hosts of the Family Sulfolobaceae

2020 ◽  
Vol 11 ◽  
Author(s):  
Ruben Michael Ceballos ◽  
Coyne Gareth Drummond ◽  
Carson Len Stacy ◽  
Elizabeth Padilla-Crespo ◽  
Kenneth Mark Stedman
Keyword(s):  
Virus Strain ◽  
The Family ◽  
Replication Strategy

scholarly journals Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruijuan Du ◽  
Chuntian Huang ◽  
Kangdong Liu ◽  
Xiang Li ◽  
Zigang Dong
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Aurora Kinase ◽  
Interacting Proteins ◽  
Multiple Tumor ◽  
Oncogenic Pathways ◽  
Wide Range ◽  
The Family ◽  
Tumor Types ◽  
Cancer Tissues

AbstractAurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

scholarly journals The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 364
Author(s):  
Jun Ma ◽  
Lulu Ma ◽  
Meiting Yang ◽  
Wei Wu ◽  
Wenhai Feng ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Rna Virus ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Live Virus ◽  
Virus Challenge ◽  
Host Interactions

Porcine reproductive and respiratory syndrome virus (PRRSV) affects the global swine industry and causes disastrous economic losses each year. The genome of PRRSV is an enveloped single-stranded positive-sense RNA of approximately 15 kb. The PRRSV replicates primarily in alveolar macrophages of pig lungs and lymphatic organs and causes reproductive problems in sows and respiratory symptoms in piglets. To date, studies on how PRRSV survives in the host, the host immune response against viral infections, and pathogenesis, have been reported. PRRSV vaccines have been developed, including inactive virus, modified live virus, attenuated live vaccine, DNA vaccine, and immune adjuvant vaccines. However, there are certain problems with the durability and effectiveness of the licensed vaccines. Moreover, the high variability and fast-evolving populations of this RNA virus challenge the design of PRRSV vaccines, and thus effective vaccines against PRRSV have not been developed successfully. As is well known, viruses interact with the host to escape the host’s immune response and then replicate and propagate in the host, which is the key to virus survival. Here, we review the complex network and the mechanism of PRRSV–host interactions in the processes of virus infection. It is critical to develop novel antiviral strategies against PRRSV by studying these host–virus interactions and structures to better understand the molecular mechanisms of PRRSV immune escape.

scholarly journals Эколого-биологическая характеристика Lactobacillus acidophilus

2017 ◽  
Vol 7 (4) ◽  
pp. 214-230 ◽  
Author(s):  
A. N. Irkitova ◽  
A. V. Matsyura
Keyword(s):  
Lactobacillus Acidophilus ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Systematic Position ◽  
New Class ◽  
Safe Level ◽  
Molecular Approaches ◽  
The Family ◽  
Long Time ◽  
Biochemical Identification

<p>Lactobacillus acidophilus - homofermentative lactobacillus, specializing in living in the gastrointestinal and urogenital tracts of mammals and birds. It accompanies a person from birth and throughout his life, providing a whole range of useful services, the main one of which is active participation in the body's defense system against the harmful action of undesirable microorganisms (preventing the growth of pathogenic bacteria and restraining populations of opportunistic microbes at a safe level) . It is this property of the acidophilus rod that explains its wide practical use in various probiotic products and preparations of dietary, medical and agricultural purposes.<br />Although the acidophilus rod is known and purposefully used for a long time, it still ha the great potential for the research. The use of gene-molecular approaches has made it possible to clarify the systematic position of L. acidophilus in the family of lactobacilli and to identify a group of closely related species, often indistinguishable by traditional physiological and biochemical identification methods. Today, the efforts of researchers are focused on elucidating the molecular mechanisms by which antagonistically active strains of L. acidophilus carry out a bactericidal and bacteriolytic effect on harmful microbes. Disclosure of these mechanisms will not only allow more efficient selection and use of strains of L. acidophilus, but also create a new class of antibiotics that are more effective and have less side effects than existing ones.<br />This review is devoted to the description of the probiotic microorganism Lactobacillus acidophilus. In the article the biological and ecological properties of the acidophilus rod are described in detail, examples of practical use of this microorganism in various branches of the national economy are given.</p>

scholarly journals Phosphoproteomic analysis of lettuce (Lactuca sativa L.) reveals starch and sucrose metabolism functions during bolting induced by high temperature

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244198
Author(s):  
Xiaoxiao Qin ◽  
Panpan Li ◽  
Shaowei Lu ◽  
Yanchuan Sun ◽  
Lifeng Meng ◽  
...  
Keyword(s):  
High Temperature ◽  
High Temperatures ◽  
Lactuca Sativa ◽  
Molecular Mechanisms ◽  
Soluble Sugar ◽  
High Temperature Stress ◽  
Temperature Treatment ◽  
Sucrose Metabolism ◽  
High Temperature Treatment ◽  
Lactuca Sativa L

High temperatures induce early bolting in lettuce (Lactuca sativa L.), which decreases both quality and production. However, knowledge of the molecular mechanism underlying high temperature promotes premature bolting is lacking. In this study, we compared lettuce during the bolting period induced by high temperatures (33/25 °C, day/night) to which raised under controlled temperatures (20/13 °C, day/night) using iTRAQ-based phosphoproteomic analysis. A total of 3,814 phosphorylation sites located on 1,766 phosphopeptides from 987 phosphoproteins were identified after high-temperature treatment,among which 217 phosphoproteins significantly changed their expression abundance (116 upregulated and 101 downregulated). Most phosphoproteins for which the abundance was altered were associated with the metabolic process, with the main molecular functions were catalytic activity and transporter activity. Regarding the functional pathway, starch and sucrose metabolism was the mainly enriched signaling pathways. Hence, high temperature influenced phosphoprotein activity, especially that associated with starch and sucrose metabolism. We suspected that the lettuce shorten its growth cycle and reduce vegetative growth owing to changes in the contents of starch and soluble sugar after high temperature stress, which then led to early bolting/flowering. These findings improve our understanding of the regulatory molecular mechanisms involved in lettuce bolting.

scholarly journals Structure-based mechanism of action of a viral poly(ADP-ribose) polymerase 1-interacting protein facilitating virus replication

IUCrJ ◽  
2018 ◽  
Vol 5 (6) ◽  
pp. 866-879 ◽  
Author(s):  
Woo-Chang Chung ◽  
Junsoo Kim ◽  
Byung Chul Kim ◽  
Hye-Ri Kang ◽  
JongHyeon Son ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Molecular Mechanisms ◽  
Lytic Replication ◽  
Transcription Activator ◽  
Interacting Protein ◽  
Murine Gammaherpesvirus ◽  
Unit Structure ◽  
Parp 1

Poly(ADP-ribose) polymerase 1 (PARP-1), an enzyme that modifies nuclear proteins by poly(ADP-ribosyl)ation, regulates various cellular activities and restricts the lytic replication of oncogenic gammaherpesviruses by inhibiting the function of replication and transcription activator (RTA), a key switch molecule of the viral life cycle. A viral PARP-1-interacting protein (vPIP) encoded by murine gammaherpesvirus 68 (MHV-68) orf49 facilitates lytic replication by disrupting interactions between PARP-1 and RTA. Here, the structure of MHV-68 vPIP was determined at 2.2 Å resolution. The structure consists of 12 α-helices with characteristic N-terminal β-strands (Nβ) and forms a V-shaped-twist dimer in the asymmetric unit. Structure-based mutagenesis revealed that Nβ and the α1 helix (residues 2–26) are essential for the nuclear localization and function of vPIP; three residues were then identified (Phe5, Ser12 and Thr16) that were critical for the function of vPIP and its interaction with PARP-1. A recombinant MHV-68 harboring mutations of these three residues showed severely attenuated viral replication both in vitro and in vivo. Moreover, ORF49 of Kaposi's sarcoma-associated herpesvirus also directly interacted with PARP-1, indicating a conserved mechanism of action of vPIPs. The results elucidate the novel molecular mechanisms by which oncogenic gammaherpesviruses overcome repression by PARP-1 using vPIPs.

scholarly journals Obesity in Childhood and Adolescence, Genetic Factors

PRILOZI ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 121-133 ◽  
Author(s):  
Marko Kostovski ◽  
Velibor Tasic ◽  
Nevena Laban ◽  
Momir Polenakovic ◽  
Dragan Danilovski ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rapid Onset ◽  
Modern World ◽  
Childhood And Adolescence ◽  
Monogenic Obesity ◽  
Wagr Syndrome ◽  
The Family ◽  
Genetic Mechanisms ◽  
Childhood And Adolescent Obesity ◽  
Carbohydrate Intolerance

AbstractObesity and excess weight are a pandemic phenomenon in the modern world. Childhood and adolescent obesity often ends up in obesity in adults. The costs of obesity and its consequences are staggering for any society, crippling for countries in development. Childhood obesity is also widespread in Macedonia. Metabolic syndrome, dyslipidemia and carbohydrate intolerance are found in significant numbers. Parents and grandparents are often obese. Some of the children are either dysmorphic, or slightly retarded. We have already described patients with Prader-Willi syndrome, Bardet-Biedl syndrome or WAGR syndrome. A genetic screening for mutations in monogenic obesity in children with early, rapid-onset or severe obesity, severe hyperphagia, hypogonadism, intestinal dysfunction, hypopigmentation of hair and skin, postprandial hypoglycaemia, diabetes insipidus, abnormal leptin level and coexistence of lean and obese siblings in the family discovers many genetic forms of obesity. There are about 30 monogenic forms of obesity. In addition, obesity is different in ethnic groups, and the types of monogenic obesity differ. In brief, an increasing number of genes and genetic mechanisms in children continue to be discovered. This sheds new light on the molecular mechanisms of obesity and potentially gives a target for new forms of treatment.

Abstract P280: CCL5 Causes Vascular Injury Via CCR5 And Nadph Oxidase 1- Derived Ros

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Shubhnita Singh ◽  
Ariane Bruder Nascimento ◽  
Anita Bargaje ◽  
Thiago Bruder Nascimento
Keyword(s):  
Vascular Injury ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Vascular Inflammation ◽  
Fold Increase ◽  
Cellular Migration ◽  
Vascular Growth ◽  
Aortic Smooth Muscle ◽  
The Family ◽  
Nadph Oxidase 1

Chemokine (C-Cmotif) ligand 5 (CCL5) and its receptor CCR5 belong to the family of chemokines and are expressed and active in the vasculature. NADPH oxidases (Noxs) are the major source of reactive oxygen species (ROS) in vascular cells, but whether the activation of these oxidases is CCL5/CCR5 sensitive and whether such interaction participates in the genesis of vascular disease is not fully known. We investigated whether CCL5/CCR5 leads to vascular injury by activating Nox1. Carotid ligation model (CL, for 2-weeks) was used to induce pathological vascular growth in 10-weeks old (C57BL6/J) mice. Rat aortic smooth muscle cells (RASMC) were treated with recombinant CCL5 (100ng/mL) to study the molecular mechanisms. CL induces neointima formation, which was associated with increase in IL1β, TNFα, CCR3, CCR5 (3-fold increase), CCL5, and Nox1 gene expression. No difference was observed for Nox2 and 4. Treatment with CCR5 blocker (maraviroc, 25mg/Kg/day i.p) partially inhibited CL-induced vascular injury (media/intima ratio, CL: 1.2 ± 0.2 vs CL + maraviroc: 0.7 ± 0.2) and Nox1 expression (Fold changes: CL: 2.1 ± 0.4 vs CL + maraviroc: 1.2 ± 0.4). In RASMC, CCL5 induced Nox1 expression, which was blunted by pre-treating cells with maraviroc (10uM). Also, it increases p47phox content in membrane fraction (index of Nox activation), and elevated ROS production, analyzed by L012. CCL5 also induced cell migration, measured by transwell assay (number of cells per spot, control: 21.3 ± 3.1 vs CCL5: 31.1 ± 2.4), proliferation, analyzed by Edu+ cells (% of cells per spot, control: 10.6 ± 4.3 vs CCL5: 22.8 ± 5.1), and inflammation (studied by IL1β and TNFα levels). Lastly, CCL5 elevated NF-κB translocation into the nucleus, indicating NF-κB activation. Strikingly, inhibition of Nox1 (GKT771, 10uM), blocked CCL5-induced vascular migration, proliferation, and inflammation, as well as NF-κB activation. We propose that CCL5 activates Nox1 in the vasculature leading to local injury characterized by vascular inflammation and cellular migration and proliferation, perhaps by activating NF-κB signaling. Herein, we place CCR5 signaling as possible therapeutic target to reduce the cardiovascular risk in inflammatory diseases associated with dysregulation of CCL5 and/or CCR5

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