scholarly journals Within-Host Phenotypic Evolution and the Population-Level Control of Chronic Viral Infections by Treatment and Prophylaxis

Mathematics ◽  
2020 ◽  
Vol 8 (9) ◽  
pp. 1500
Author(s):  
Dmitry Gromov ◽  
Ethan O. Romero-Severson
Keyword(s):  
Viral Infections ◽  
Sequence Data ◽  
Phenotypic Diversity ◽  
Evolutionary Process ◽  
Population Level ◽  
Mathematical Framework ◽  
Phenotypic Evolution ◽  
Level Control ◽  
Chronic Viral Infections ◽  
Prophylactic Measures

Chronic viral infections can persist for decades spanning thousands of viral generations, leading to a highly diverse population of viruses with its own complex evolutionary history. We propose an expandable mathematical framework for understanding how the emergence of genetic and phenotypic diversity affects the population-level control of those infections by both non-curative treatment and chemo-prophylactic measures. Our frameworks allows both neutral and phenotypic evolution, and we consider the specific evolution of contagiousness, resistance to therapy, and efficacy of prophylaxis. We compute both the controlled and uncontrolled, population-level basic reproduction number accounting for the within-host evolutionary process where new phenotypes emerge and are lost in infected persons, which we also extend to include both treatment and prophylactic control efforts. We used these results to discuss the conditions under which the relative efficacy of prophylactic versus therapeutic methods of control are superior. Finally, we give expressions for the endemic equilibrium of these models for certain constrained versions of the within-host evolutionary model providing a potential method for estimating within-host evolutionary parameters from population-level genetic sequence data.

Blood-Borne Chronic Viral Infections in a Large Cohort of Immigrants in Southern Italy

2019 ◽  
Author(s):  
Nicola Coppola ◽  
Caterina Monari ◽  
Loredana Alessio ◽  
Lorenzo Onorato ◽  
Luciano Gualderi ◽  
...  
Keyword(s):  
Southern Italy ◽  
Viral Infections ◽  
Large Cohort ◽  
Chronic Viral Infections

scholarly journals Reef development and Sea level changes drive Acanthaster Population Expansion in the Indo-Pacific region

2020 ◽  
Author(s):  
P.C. Pretorius ◽  
T.B. Hoareau
Keyword(s):  
Population Size ◽  
Sea Level ◽  
Environmental Changes ◽  
Sequence Data ◽  
Demographic History ◽  
Population Expansion ◽  
Population Level ◽  
Sea Level Changes ◽  
Reef Development ◽  
Curve Fitting Method

AbstractMolecular clock calibration is central in population genetics as it provides an accurate inference of demographic history, whereby helping with the identification of driving factors of population changes in an ecosystem. This is particularly important for coral reef species that are seriously threatened globally and in need of conservation. Biogeographic events and fossils are the main source of calibration, but these are known to overestimate timing and parameters at population level, which leads to a disconnection between environmental changes and inferred reconstructions. Here, we propose the Last Glacial Maximum (LGM) calibration that is based on the assumptions that reef species went through a bottleneck during the LGM, which was followed by an early yet marginal increase in population size. We validated the LGM calibration using simulations and genetic inferences based on Extended Bayesian Skyline Plots. Applying it to mitochondrial sequence data of crown-of-thorns starfish Acanthaster spp., we obtained mutation rates that were higher than phylogenetically based calibrations and varied among populations. The timing of the greatest increase in population size differed slightly among populations, but all started between 10 and 20 kya. Using a curve-fitting method, we showed that Acanthaster populations were more influenced by sea-level changes in the Indian Ocean and by reef development in the Pacific Ocean. Our results illustrate that the LGM calibration is robust and can probably provide accurate demographic inferences in many reef species. Application of this calibration has the potential to help identify population drivers that are central for the conservation and management of these threatened ecosystems.

scholarly journals How development affects evolution

2021 ◽  
Author(s):  
Mauricio González-Forero ◽  
Andy Gardner
Keyword(s):  
Niche Construction ◽  
Fitness Landscape ◽  
Stabilizing Selection ◽  
Mathematical Framework ◽  
Phenotypic Evolution ◽  
Landscape Development ◽  
Developmental Constraints ◽  
Evolutionary Pathway ◽  
Punctuated Equilibria ◽  
Adaptive Radiations

How development affects evolution. A mathematical framework that explicitly integrates development into evolution has recently been derived. Here we use this framework to analyse how development affects evolution. We show that, whilst selection pushes genetic and phenotypic evolution uphill on the fitness landscape, development determines the admissible evolutionary pathway, such that evolutionary outcomes occur at path peaks, which need not be peaks of the fitness landscape. Development can generate path peaks, triggering adaptive radiations, even on constant, single-peak landscapes. Phenotypic plasticity, niche construction, extra-genetic inheritance, and developmental bias variously alter the evolutionary path and hence the outcome. Selective development, whereby phenotype construction may point in the adaptive direction, may induce evolution either towards or away landscape peaks depending on the developmental constraints. Additionally, developmental propagation of phenotypic effects over age allows for the evolution of negative senescence. These results help explain empirical observations including punctuated equilibria, the paradox of stasis, the rarity of stabilizing selection, and negative senescence, and show that development has a major role in evolution.

scholarly journals Aging and Options to Halt Declining Immunity to Virus Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Miguel Ángel Palacios-Pedrero ◽  
Albert D. M. E. Osterhaus ◽  
Tanja Becker ◽  
Husni Elbahesh ◽  
Guus F. Rimmelzwaan ◽  
...  
Keyword(s):  
Older Adults ◽  
Immune System ◽  
Immune Function ◽  
Adaptive Immunity ◽  
Bacterial Infections ◽  
Viral Infections ◽  
Age Group ◽  
Virus Infections ◽  
Innate And Adaptive Immunity ◽  
Chronic Viral Infections

Immunosenescence is a process associated with aging that leads to dysregulation of cells of innate and adaptive immunity, which may become dysfunctional. Consequently, older adults show increased severity of viral and bacterial infections and impaired responses to vaccinations. A better understanding of the process of immunosenescence will aid the development of novel strategies to boost the immune system in older adults. In this review, we focus on major alterations of the immune system triggered by aging, and address the effect of chronic viral infections, effectiveness of vaccination of older adults and strategies to improve immune function in this vulnerable age group.

scholarly journals A narrative review on HPV vaccination among boys and men

2020 ◽  
pp. 9-12
Author(s):  
Vinod K Ramani ◽  
Radheshyam Naik
Keyword(s):  
Hpv Vaccine ◽  
Hpv Vaccination ◽  
Herd Immunity ◽  
Population Level ◽  
Hpv Infection ◽  
Level Control ◽  
Anogenital Warts ◽  
Indian Context ◽  
Present Generation ◽  
The Cost

Apart from cervical cancer, Human papillomavirus (HPV) infection is associated with head and neck as well as other anogenital cancers such as vulva, vagina, anus, and penis. HPV vaccine provides specific protection against the disease and its subsequent manifestations.Vaccination programs for men tend to improve population-level control of HPV infection and directly prevent HPV related disease such as anogenital warts and oropharyngeal cancers in males. HPV vaccine does not treat existing infection or lesions/cancer and is intended for individuals before initiation fo sexual activity or any other form of exposure to HPV.Many programs across the globe do not include vaccination for boys because of the cost and little recognition of the emerging epidemic of HPV associated cancers in men. In the Indian context, as screening is not feasible for non-cervical HPV associated cancers, its incidence mostly among men will continue to rise until the present generation of vaccinated adolescents reaches their middle-age.Vaccination will reduce transmission rates and increase herd immunity. This in-turn, will prevent not just cervical cancers but also other HPV-associated malignancies among men and women.

scholarly journals Complementary Effects of Interleukin-15 and Alpha Interferon Induce Immunity in Hepatitis B Virus Transgenic Mice

2016 ◽  
Vol 90 (19) ◽  
pp. 8563-8574 ◽  
Author(s):  
Marianna Di Scala ◽  
Itziar Otano ◽  
Irene Gil-Fariña ◽  
Lucia Vanrell ◽  
Mirja Hommel ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
T Cell ◽  
Hepatitis B ◽  
Transgenic Mice ◽  
Chronic Hepatitis B ◽  
Viral Infections ◽  
Chronic Viral Infections ◽  
B Virus ◽  
Interleukin 15

ABSTRACTIn chronic hepatitis B (CHB), failure to control hepatitis B virus (HBV) is associated with T cell dysfunction. HBV transgenic mice mirror many features of the human disease, including T cell unresponsiveness, and thus represent an appropriate model in which to test novel therapeutic strategies. To date, the tolerant state of CD8+T cells in these animals could be altered only by strong immunogens or by immunization with HBV antigen-pulsed dendritic cells; however, the effectors induced were unable to suppress viral gene expression or replication. Because of the known stimulatory properties of alpha interferon (IFN-α) and interleukin-15 (IL-15), this study explored the therapeutic potential of liver-directed gene transfer of these cytokines in a murine model of CHB using adeno-associated virus (AAV) delivery. This combination not only resulted in a reduction in the viral load in the liver and the induction of an antibody response but also gave rise to functional and specific CD8+immunity. Furthermore, when splenic and intrahepatic lymphocytes from IFN-α- and IL-15-treated animals were transferred to new HBV carriers, partial antiviral immunity was achieved. In contrast to previous observations made using either cytokine alone, markedly attenuated PD-L1 induction in hepatic tissue was observed upon coadministration. An initial study with CHB patient samples also gave promising results. Hence, we demonstrated synergy between two stimulating cytokines, IL-15 and IFN-α, which, given together, constitute a potent approach to significantly enhance the CD8+T cell response in a state of immune hyporesponsiveness. Such an approach may be useful for treating chronic viral infections and neoplastic conditions.IMPORTANCEWith 350 million people affected worldwide and 600,000 annual deaths due to HBV-induced liver cirrhosis and/or hepatocellular carcinoma, chronic hepatitis B (CHB) is a major health problem. However, current treatment options are costly and not very effective and/or need to be administered for life. The unprecedented efficacy of the strategy described in our paper may offer an alternative and is relevant for a broad spectrum of readers because of its clear translational importance to other chronic viral infections in which a hyporesponsive antigen-specific T cell repertoire prevents clearance of the pathogen.

scholarly journals GB Virus C E2 Inhibits PD-1-Mediated T Cell Signaling Dysfunction during Chronic Viral Infection

Proceedings ◽  
2020 ◽  
Vol 50 (1) ◽  
pp. 62
Author(s):  
Nirjal Bhattarai ◽  
Jennifer L. Welch ◽  
Jinhua Xiang ◽  
Muthu Saravanan Manoharan ◽  
Jeffrey A. Martinson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Viral Infections ◽  
Activated T Cells ◽  
E2 Protein ◽  
Gb Virus C ◽  
Cell Dysfunction ◽  
Chronic Viral Infections ◽  
T Cell Dysfunction ◽  
Virus C

Background: Program death receptor 1 (PD-1) is a co-inhibitory receptor that is upregulated and contributes to T cell dysfunction (exhaustion) during chronic viral infections, including HIV and HCV. GB virus C (GBV-C) is a persistent human virus, and co-infection is associated with reduced immune activation and improved clinical outcomes in HIV- and Ebola-infected individuals. Methods: PD-1 levels were measured by flow cytometry on CD38+ T cells from 45 HIV-infected individuals, 20 of whom were co-infected with GBV-C. Jurkat cell lines that stably express GBV-C E2 protein and vector control were used to purify total cellular RNA before, and 24 h following, activation using anti-CD3/CD28 treatment. Gene expression was analyzed by RNA-seq and qRT-PCR. Results: HIV-infected individuals with GBV-C viremia had reduced PD-1 expression on activated CD4+ and CD8+ T cells compared to HIV-infected GBV-C negative individuals. GBV-C particles and GBV-C E2 protein each inhibited PD-1 expression on T cells in vitro. Consistent with this, GBV-C E2 reduced gene expression of PD-1, and its ligand PD-L1, in both resting and activated T cells. GBV-C E2 regulated transcription of the PD-1 signaling pathway and T cell activation associated genes, without downregulation of the interferon-stimulated and innate immunity-related genes needed to resolve viral infections. Conclusions: Our current understanding of chronic RNA virus infections is that upregulation of PD-1 with T cell exhaustion is critical for viral persistence. However, these data demonstrate that GBV-C infection reduced PD-1 expression on activated T cells during HIV infection, and that the GBV-C E2 protein inhibits PD-1 signaling in T cells. This may preserve T cell function and contribute to the lack of immune deficiency in people with chronic GBV-C infection. Understanding the mechanisms by which GBV-C E2 alters PD-1 signaling may aid in the development of novel immunomodulatory therapeutics to prevent T cell dysfunction (exhaustion) during chronic viral infections.

scholarly journals AGING WITH HEMOPHILIA: THE CHALLENGE OF APPROPRIATE DRUG PRESCRIPTION

2019 ◽  
Vol 11 (1) ◽  
pp. e2019056 ◽  
Author(s):  
Pier Mannuccio Mannucci
Keyword(s):  
Viral Infections ◽  
Population Aging ◽  
Drug Prescription ◽  
Daily Intake ◽  
Cross Sectional ◽  
Inappropriate Drugs ◽  
Chronic Viral Infections ◽  
Related Risk ◽  
Hemophilia Treatment Centers ◽  
Drugs Interaction

In high-income countries persons with severe hemophilia (PWH) A and B are aging, like their age-matched peers without hemophilia from the general population. Aging is associated not only with the comorbidities stemming from their inherited bleeding disorder (arthropathy, chronic viral infections such as hepatitis and AIDS) but also with the multiple chronic ailments associated with aging (cancer, cardiovascular disease, COPD).  Multimorbidity is inevitably associated with polypharmacy, i.e., the chronic daily intake of at least five drugs, and with the related risk of severe adverse events associated with the use of inappropriate drugs and drug-drug interactions. Information on the pattern of drug prescription and usage by PWH is relatively scanty, but on the whole, the available data indicate that the rate of polypharmacy, as well as the risk of drug-drug interaction, is relatively low in PWH and better than that in their age peers without hemophilia followed by general practitioners. It is believed that this advantage results from the collaborative coordination on drug prescribing exerted, through their integration with practitioners and organ specialists, by specialized hemophilia treatment centers in the frame of comprehensive care programs. However, the available cross-sectional data were mainly obtained in relatively young PWH, so that there is a need to obtain more accurate data from the ongoing prospective studies that are being carried out in more and more progressively aging PWH.    Keywords: Hemophilia; Aging; Comorbidity; Drugs Interaction.  

scholarly journals Recurrent hybridization underlies the evolution of novelty in Gentiana (Gentianaceae) in the Qinghai-Tibetan Plateau

AoB Plants ◽  
2020 ◽  
Author(s):  
Peng-Cheng Fu ◽  
Alex D Twyford ◽  
Shan-Shan Sun ◽  
Hong-Yu Wang ◽  
Ming-Ze Xia ◽  
...  
Keyword(s):  
Tibetan Plateau ◽  
Sequence Data ◽  
Evolutionary Process ◽  
Source Area ◽  
Nuclear Data ◽  
Population History ◽  
Plastid Genomes ◽  
Key Factor ◽  
History Of ◽  
Postglacial Expansion

Abstract The Qinghai-Tibetan Plateau (QTP) and adjacent areas are centers of diversity for several alpine groups. Although the QTP acted as a source area for diversification of the alpine genus Gentiana, the evolutionary process underlying diversity in this genus, especially the formation of narrow endemics, is still poorly understood. Hybridization has been proposed as a driver of plant endemism in the QTP but few cases have been documented with genetic data. Here, we describe a new endemic species in Gentiana section Cruciata as G. hoae sp. nov., and explore its evolutionary history with complete plastid genomes and nuclear ribosomal ITS sequence data. Genetic divergence within G. hoae approximately 3 million years ago was followed by postglacial expansion on the QTP, suggesting Pleistocene glaciations as a key factor shaping the population history of G. hoae. Furthermore, a mismatch between plastid and nuclear data suggest that G. hoae participated in historical hybridization, while population sequencing show this species continues to hybridize with the co-occurring congener G. straminea in three locations. Our results indicate that hybridization may be a common process in the evolution of Gentiana and may be widespread among recently diverged taxa of the QTP.

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