scholarly journals Characterization of Symbiodinium-associated viruses and implications for coral health

2021 ◽  
Author(s):  
◽  
Scott Anthony Lawrence
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Cell Cultures ◽  
Viral Infections ◽  
Lytic Cycle ◽  
Symbiodinium Cell ◽  
Coral Diseases ◽  
Expression Levels ◽  
Virus Like Particles ◽  
Chronic Viral Infections

<p>Coral reefs are in decline worldwide. Much of this decline is attributable to mass coral bleaching events and disease outbreaks, both of which are linked to anthropogenic climate change. Despite increased research effort, much remains unknown about these phenomena, especially the causative agents of many coral diseases. In particular, coral-associated viruses have received little attention, and their potential roles in coral diseases are largely unknown. This study aimed to address this lack of information by characterising the viruses associated with reef-building corals and Symbiodinium (dinoflagellates that can form symbioses with corals).  Symbiodinium virus screening experiments revealed the presence of numerous and varied virus-like particles (VLPs) inside cells. Of the 49 Symbiodinium cultures screened, approximately one third contained putative latent viral infections that could be induced to enter their lytic cycle by UV irradiation. Electron microscope examination revealed VLPs closely resembling viruses previously found in dinoflagellates and other microalgae. Three cultures that showed evidence of latent viral infections were chosen for whole transcriptome sequencing, which revealed the presence of viral genes that were expressed in several different types of Symbiodinium. The relationship between the detected genes and known viral gene sequences suggested that the cells were infected with double-stranded DNA (dsDNA) viruses.  In order to determine how the host cell responds to stress-induced viral infection, the expression levels of genes associated with stress response and viral infection were measured. The expression levels of many genes were unchanged following UV stress, and expression of genes that were predicted to be upregulated following stress, such as those encoding antioxidant enzymes, in fact showed lower expression levels. Despite this, several groups of genes involved in viral infection and host cell response were upregulated following stress, providing further evidence for stress-induced latent or chronic viral infections.  In addition to the research carried out on Symbiodinium cell cultures, viruses associated with three coral diseases were studied using electron microscopy. Virus-like particles were present in coral and Symbiodinium cells from all three diseases, but viral abundance was correlated with disease state in only one: white patch syndrome (WPS) of Porites australiensis. The locations and morphologies of the VLPs associated with WPS suggested the presence of dsDNA and single-stranded RNA (ssRNA) viruses infecting both the coral animal and Symbiodinium cells. DNA sequences obtained from WPS-affected corals matched closely with sequences obtained from VLP-containing Symbiodinium cells. Based on the evidence gathered from Symbiodinium cell cultures and coral tissues, I propose a theoretical model of viral infection in WPS. In this model, the coral animal cells are routinely subject to chronic viral infections, and Symbiodinium cells harbour two types of chronic or latent infections – a dsDNA and an ssRNA virus – that can be induced via stress, resulting in cell lysis or loss of the cells from the coral host.  In addition to detection and rudimentary identification of viruses infecting Symbiodinium cells, this study generated the largest dinoflagellate transcriptomic dataset to date. These data will prove valuable for future research into Symbiodinium, both in terms of viral infections and more generally.</p>

scholarly journals Characterization of Symbiodinium-associated viruses and implications for coral health

2021 ◽  
Author(s):  
◽  
Scott Anthony Lawrence
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Cell Cultures ◽  
Viral Infections ◽  
Lytic Cycle ◽  
Symbiodinium Cell ◽  
Coral Diseases ◽  
Expression Levels ◽  
Virus Like Particles ◽  
Chronic Viral Infections

<p>Coral reefs are in decline worldwide. Much of this decline is attributable to mass coral bleaching events and disease outbreaks, both of which are linked to anthropogenic climate change. Despite increased research effort, much remains unknown about these phenomena, especially the causative agents of many coral diseases. In particular, coral-associated viruses have received little attention, and their potential roles in coral diseases are largely unknown. This study aimed to address this lack of information by characterising the viruses associated with reef-building corals and Symbiodinium (dinoflagellates that can form symbioses with corals).  Symbiodinium virus screening experiments revealed the presence of numerous and varied virus-like particles (VLPs) inside cells. Of the 49 Symbiodinium cultures screened, approximately one third contained putative latent viral infections that could be induced to enter their lytic cycle by UV irradiation. Electron microscope examination revealed VLPs closely resembling viruses previously found in dinoflagellates and other microalgae. Three cultures that showed evidence of latent viral infections were chosen for whole transcriptome sequencing, which revealed the presence of viral genes that were expressed in several different types of Symbiodinium. The relationship between the detected genes and known viral gene sequences suggested that the cells were infected with double-stranded DNA (dsDNA) viruses.  In order to determine how the host cell responds to stress-induced viral infection, the expression levels of genes associated with stress response and viral infection were measured. The expression levels of many genes were unchanged following UV stress, and expression of genes that were predicted to be upregulated following stress, such as those encoding antioxidant enzymes, in fact showed lower expression levels. Despite this, several groups of genes involved in viral infection and host cell response were upregulated following stress, providing further evidence for stress-induced latent or chronic viral infections.  In addition to the research carried out on Symbiodinium cell cultures, viruses associated with three coral diseases were studied using electron microscopy. Virus-like particles were present in coral and Symbiodinium cells from all three diseases, but viral abundance was correlated with disease state in only one: white patch syndrome (WPS) of Porites australiensis. The locations and morphologies of the VLPs associated with WPS suggested the presence of dsDNA and single-stranded RNA (ssRNA) viruses infecting both the coral animal and Symbiodinium cells. DNA sequences obtained from WPS-affected corals matched closely with sequences obtained from VLP-containing Symbiodinium cells. Based on the evidence gathered from Symbiodinium cell cultures and coral tissues, I propose a theoretical model of viral infection in WPS. In this model, the coral animal cells are routinely subject to chronic viral infections, and Symbiodinium cells harbour two types of chronic or latent infections – a dsDNA and an ssRNA virus – that can be induced via stress, resulting in cell lysis or loss of the cells from the coral host.  In addition to detection and rudimentary identification of viruses infecting Symbiodinium cells, this study generated the largest dinoflagellate transcriptomic dataset to date. These data will prove valuable for future research into Symbiodinium, both in terms of viral infections and more generally.</p>

scholarly journals A Combination of Anti-PD-L1 Treatment and Therapeutic Vaccination Facilitates Improved Retroviral Clearance via Reactivation of Highly Exhausted T Cells

mBio ◽  
2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Torben Knuschke ◽  
Sebastian Kollenda ◽  
Christina Wenzek ◽  
Gennadiy Zelinskyy ◽  
Philine Steinbach ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Combination Therapy ◽  
Viral Infection ◽  
Viral Infections ◽  
T Cell Immunity ◽  
Chronic Viral Infection ◽  
Therapeutic Vaccination ◽  
Chronic Viral Infections ◽  
Cell Immunity

ABSTRACT PD-1-targeted therapies have shown modest antiviral effects in preclinical models of chronic viral infection. Thus, novel therapy protocols are necessary to enhance T cell immunity and viral control to overcome T cell dysfunction and immunosuppression. Here, we demonstrate that nanoparticle-based therapeutic vaccination improved PD-1-targeted therapy during chronic infection with Friend retrovirus (FV). Prevention of inhibitory signals by blocking PD-L1 in combination with therapeutic vaccination with nanoparticles containing the microbial compound CpG and a CD8+ T cell Gag epitope peptide synergistically enhanced functional virus-specific CD8+ T cell responses and improved viral clearance. We characterized the CD8+ T cell populations that were affected by this combination therapy, demonstrating that new effector cells were generated and that exhausted CD8+ T cells were reactivated at the same time. While CD8+ T cells with high PD-1 (PD-1hi) expression turned into a large population of granzyme B-expressing CD8+ T cells after combination therapy, CXCR5-expressing follicular cytotoxic CD8+ T cells also expanded to a high degree. Thus, our study describes a very efficient approach to enhance virus control and may help us to understand the mechanisms of combination immunotherapy reactivating CD8+ T cell immunity. A better understanding of CD8+ T cell immunity during combination therapy will be important for developing efficient checkpoint therapies against chronic viral infections and cancer. IMPORTANCE Despite significant efforts, vaccines are not yet available for every infectious pathogen, and the search for a protective approach to prevent the establishment of chronic infections, i.e., with HIV, continues. Immune checkpoint therapies targeting inhibitory receptors, such as PD-1, have shown impressive results against solid tumors. However, immune checkpoint therapies have not yet been licensed to treat chronic viral infections, since a blockade of inhibitory receptors alone provides only limited benefit, as demonstrated in preclinical models of chronic viral infection. Thus, there is a high interest in the development of potent combination immunotherapies. Here, we tested whether the combination of a PD-L1 blockade and therapeutic vaccination with functionalized nanoparticles is a potent therapy during chronic Friend retrovirus infection. We demonstrate that the combination therapy induced a synergistic reinvigoration of the exhausted virus-specific CD8+ T cell immunity. Taken together, our results provide further information on how to improve PD-1-targeted therapies during chronic viral infection and cancer.

scholarly journals Redox Imbalance and Viral Infections in Neurodegenerative Diseases

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Dolores Limongi ◽  
Sara Baldelli
Keyword(s):  
Neurodegenerative Diseases ◽  
Viral Infection ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Second Messengers ◽  
Chronic Viral Infections ◽  
Ros Accumulation ◽  
Simplex Virus

Reactive oxygen species (ROS) are essential molecules for many physiological functions and act as second messengers in a large variety of tissues. An imbalance in the production and elimination of ROS is associated with human diseases including neurodegenerative disorders. In the last years the notion that neurodegenerative diseases are accompanied by chronic viral infections, which may result in an increase of neurodegenerative diseases progression, emerged. It is known in literature that enhanced viral infection risk, observed during neurodegeneration, is partly due to the increase of ROS accumulation in brain cells. However, the molecular mechanisms of viral infection, occurring during the progression of neurodegeneration, remain unclear. In this review, we discuss the recent knowledge regarding the role of influenza, herpes simplex virus type-1, and retroviruses infection in ROS/RNS-mediated Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS).

scholarly journals The Pattern of viral seromarkers in patients with elevated plasma creatinine of ≥ 3.5mg/dl

2020 ◽  
Vol 3 (2) ◽  
pp. 366-369
Author(s):  
Mathew Folaranmi Olaniyan ◽  
Tolulope Busayo Ojediran ◽  
Donatus FN Ozuruoke
Keyword(s):  
Renal Disease ◽  
Viral Infection ◽  
Viral Infections ◽  
Plasma Creatinine ◽  
Elevated Plasma ◽  
Point Of Entry ◽  
Chronic Viral Infections ◽  
Organ Failures ◽  
Study Population ◽  
Elevated Creatinine

Introduction: Viral seromarkers are expressed in the serum or plasma to indicate viral infection while chronic viral infections may lead to organ failures and also kidneys have receptors as a point of entry for some viruses. This work was therefore designed to characterize viral seromarkers in patients with elevated plasma creatinine of ≥ 3.5mg/dl to determine the possible contribution of viral infections to renal disease as elevated creatinine is an index of renal disease.Materials and Methods: The study population included 62 patients aged 41 – 75 years with elevated plasma creatinine of 3.9± 0.4 mg/dl as test subjects and 100 age-matched volunteers with normal plasma creatinine of 0.8±0.2mg/dl as control subjects. Anti-HCV, HBsAg, HBeAg, and HIV; HIVp24Ag/Ab were determined in the subjects by ELISA while plasma creatinine was measured by spectrophotometry.Results: The viral seromarkers obtained in the subjects include:14.5%(09) Anti-HCV; 4.8%(03) p24Ag/Ab; 22.3%(14) HBsAg and 25%(16) HBeAb in the patients with plasma creatinine of 3.9 ± 0.4 mg/dl while 5%(05) Anti-HCV; 2%(02) p24Ag/Ab ; 12%(12) HBsAg and 18%(18) HBeAb were obtained in subjects with plasma creatinine of 0.8±0.2mg/dl. Conclusions:  There was a significant relationship between viral infection and renal disease (suggested by elevated plasma creatinine) as the expression of viral seromarkers of antiHCV, HBsAg, HBeAg, and HIV; HIVp24Ag/Ab in this work were more in patients with plasma creatinine of 3.9 ± 0.4 mg/dl than subjects with plasma creatinine of 0.8±0.2mg/dl while HBsAg and HBeAg were found to be more frequent.

Real-world outcomes of treatment with immune checkpoint inhibitors in unique patient cohorts: Elderly, non-caucasian race, poor performance status, obese, chronic viral infections, and autoimmune diseases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2641-2641
Author(s):  
Neil J. Shah ◽  
Shuo Wang ◽  
Aquino Williams ◽  
Melinda Weber ◽  
Brittany Sinclaire ◽  
...  
Keyword(s):  
Viral Infection ◽  
Real World ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Viral Infections ◽  
Checkpoint Inhibitors ◽  
Chronic Viral Infection ◽  
Poor Performance Status ◽  
Chronic Viral Infections ◽  
Ecog Ps

2641 Background: Immune Checkpoint Inhibitors (ICI) have revolutionized current cancer treatment. Nevertheless, outcomes data across various patient cohorts are lacking. To address this knowledge gap, we conducted a comprehensive analysis of real-world data (RWD) that included patient cohorts traditionally underrepresented in clinical trials. Methods: We identified patients (pts) treated with ICI (anti-CTLA-4, anti-PD(L)1 or their combination at 6 US academic and community hospitals from 1/2011 – 4/2018. Clinical data obtained from EHR and CTCAE V4.03 was used to define immune-related adverse events (irAEs). Results: A total of 1332 pts treated with 1443 unique ICI treatments were included in the cohort. The median age was 66 (21-87), Male 58% (827), Caucasian 70% (1004), African American (AA) 16% (232), other race 14% (207), ECOG PS 0,1 79% (1130), chronic viral infection 5% [hepatitis B (24), hepatitis C (32) and HIV (17)], with BMI > 30 22% (287) and autoimmune disease (AID) 15% (215). Lung cancer (NSCLC) 34% (423), and melanoma 27% (389) were top 2 tumor types and nivolumab 38% (544), pembrolizumab 23% (332), and ipilimumab plus nivolumab 12% (180) were the most common ICI treatments. Overall survival (OS) was worse for patients with ECOG ≥2 (0.34 - 0.63) vs. ECOG 0,1 (1.27 - 1.73, P <0.001), and better with AID (1.21 - 2.63) vs. no AID ( 0.90 - 1.24, P=0.01) and Caucasian (1.02 - 1.45) vs AA (0.72 - 1.30, P=0.02). No difference in OS was noted for sex, other races, h/o chronic viral infection or obesity. We performed an analysis of OS and irAEs restricted to NSCLC patients (n=423); (N=447 unique ICI treatments); age >75 27% (120), AA 28% (124), Female 50% (224), ECOG PS ≥2 23% (104), BMI >30 15% (62), chronic viral infections 10% (44), and AID 14% (62). The ICI therapies were nivolumab 55% (245), pembrolizumab 23% (102), and atezolizumab 6% (27) and 16% (others). Data is contained in the table. Conclusions: Overall, in our RWD, OS appeared to be similar across above cohorts except poor OS for pts with ECOG ≥2. irAEs also appeared to be similar across cohorts except less with ECOG ≥2. In NSCLC cohort, we noted similar findings except less irAEs in Male cohort. Prospective studies are needed to confirm the above findings.[Table: see text]

scholarly journals Transcriptome and Coronavirus: New Hope and Therapy

2020 ◽  
Vol 11 (2) ◽  
pp. 9541-9552
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Genome Size ◽  
Viral Entry ◽  
Viral Infections ◽  
Cell Transformation ◽  
In Vitro Study ◽  
Cell Protein ◽  
Transformation Mechanism

Transcriptome refers to all RNA particles occur inside one cell or inside numerous cells in one organ. Coronaviruses are a family of correlated viruses that induce viral infection. In humans, coronaviruses induce respiratory viral infections that may be mild or dangerous. The coronavirus shape is large circular elements that have round tip outbreaks - the virus diameter particles=120 nm. The RNA viral genome occurs in coronavirus. The coronavirus genome size = 27-34 kilobases, and this size is the largest RNA genome size. The Life cycle of coronavirus includes viral entry, replication, and release. Coronavirus transmission was done through the connection of its protein with host cell receptors in a specific process. There are 4 types of coronavirus genus: (1) Alphacoronavirus, (2) Betacoronavirus, (3) Gammacoronavirus, and (4) Deltacoronavirus. Viral replication, immune evasion, and virion biogenesis correlated with host cell transformation mechanism. Viral molecular mechanism hijacks the host cell protein production mechanism. There is an important host factor (CPSF6) that connects with nuclear protein (NP1). The CPSF6 increases the nuclear production of NP1 in the same time, CPSF6 possesses an important role in the progress of capsid mRNAs inside the nucleus. In a viral infection, there is an increase in mRNA, myeloid differentiation 2-related lipid recognition protein (ML), and Niemann Pick-type C1 (NPC1) genes. Coronavirus is capable of replicating in in vitro study and causes lower transcriptomic variations before 12 h after viral infection. As infection progress, coronavirus causes a significant dysregulation of the host transcriptome greater than the SARS virus. In conclusion, future transcriptome studies are the basis for detecting coronavirus in the human host and for developing a specific preventive and therapeutic method for the virus.

scholarly journals Conceptual foundations of pharmacoeconomic analysis of prevention technologies of chronic viral infections

2019 ◽  
pp. 35-43
Author(s):  
S. O. Soloviov ◽  
I. V. Dziublyk ◽  
V. V. Trokhymchuk
Keyword(s):  
Viral Infection ◽  
Information Technologies ◽  
Viral Infections ◽  
Pharmacoeconomic Analysis ◽  
Optimal Strategies ◽  
Optimal Level ◽  
Pharmacoeconomic Evaluation ◽  
Cost Utility ◽  
Unified Model ◽  
Chronic Viral Infections

The introduction of various technologies for the prevention of chronic viral infections into practice requires well-founded evidence of their effectiveness, which can be obtained using pharmacoeconomic methods and models that determine not only the effectiveness and feasibility of introducing preventive technologies, but also the socio-economic associated consequences. In this context, the development of a unified model for the pharmacoeconomic evaluation of medical technologies at all stages of the prevention of chronic viral infections is key to implementing optimal strategies for combating them for both individual groups and the entire population, developing recommendations for the rational use of diagnostic tests and viral vaccines, and determining the optimal level of pharmaceutical care for patients. The aim of the work – development of a conceptual model of pharmacoeconomic analysis of technologies for the prevention of chronic viral infections. Pharmacoeconomic evaluation of technologies for the prevention of chronic viral infections is possible on the basis of an analytical platform that determines the relationship between the target population to be prevented, and the effectiveness of intermediate and final results. The pharmacoeconomic analysis of technologies for the prevention of socially significant chronic viral infections was proposed to be carried out according to the developed algorithm. Implementation of the proposed algorithm for pharmacoeconomic analysis of various technologies for the prevention of chronic viral infections was based on developed unified model of the spread of viral infection in the population, where individuals can be assigned to different clinical and epidemiological classes. This model was a combination of epidemiological and clinical prognostic approaches and can be used to predict and conduct pharmacoeconomic assessment of viral infection prevention technologies with a general decrease in the number of people in a particular epidemiological class when applying medical technology for a certain period of time. The presented concept allows to formulate the principles of pharmacoeconomic evaluation of technologies for the prevention of chronic viral infections. It was advisable to use the concept of quality of life in assessing the usefulness of the technologies under study, which allows to formalize the cost-utility coefficient, minimization of which determines pharmacoeconomic reasonable strategies for the prevention of chronic viral infections. The developed concept is promising, and information technologies based on it can become a reliable source of information to support decision-making by health experts in the pharmacoeconomic evaluation of technologies for the prevention of chronic viral infections.

scholarly journals Molecular features similarities between SARS-CoV-2, SARS, MERS and key human genes could favour the viral infections and trigger collateral effects

2020 ◽  
Author(s):  
Lucas L. Maldonado ◽  
Laura Kamenetzky
Keyword(s):  
Viral Infection ◽  
Host Cell ◽  
Viral Infections ◽  
Human Genetics ◽  
High Rate ◽  
Genetic Population ◽  
Molecular Features ◽  
Human Genes ◽  
Viral Genes ◽  
Collateral Effects

AbstractIn December 2019 rising pneumonia cases caused by a novel β-coronavirus (SARS-CoV-2) occurred in Wuhan, China, which has rapidly spread worldwide causing thousands of deaths. The WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern therefore several scientists are dedicated to the study of the new virus. Since human viruses have codon usage biases that match highly expressed proteins in the tissues they infect and depend on host cell machinery for replication and co-evolution, we selected the genes that are highly expressed in the tissue of human lungs to perform computational studies that permit to compare their molecular features with SARS, SARS-CoV-2 and MERS genes. In our studies, we analysed 91 molecular features for 339 viral genes and 463 human genes that consisted of 677873 codon positions. Hereby, we found that A/T bias in viral genes could propitiate the viral infection favoured by a host dependant specialization using the host cell machinery of only some genes. The envelope protein E, the membrane glycoprotein M and ORF7 could have been further benefited by a high rate of A/T in the third codon position. Thereby, the mistranslation or de-regulation of protein synthesis could produce collateral effects, as a consequence of viral occupancy of the host translation machinery due tomolecular similarities with viral genes. Furthermore, we provided a list of candidate human genes whose molecular features match those of SARS-CoV-2, SARSand MERS genes, which should be considered to be incorporated into genetic population studies to evaluate thesusceptibility to respiratory viral infections caused by these viruses. The results presented here, settle the basis for further research in the field of human genetics associated with the new viral infection, COVID-19, caused by SARS-CoV-2 and for the development of antiviral preventive methods.

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