A modeling approach for adaptive evolution marguerite a. Molecular biology and evolution oxford university press. Coupled within host and betweenhost dynamics and evolution of virulence part i. Mathematically modeling hiv drug pharmacodynamics date. Debilitated viral clones often gain fitness even when subjected to considerable bottlenecking novella et al. Modules for simulating hivsti transmission dynamics among men who have sex with men and heterosexual populations, developed as an extension to our general networkbased epidemic modeling platform, epimodel. Modeling and managing the evolutionary component of. Epimodel and epimodelhiv use the statistical framework of temporal exponentialfamily random graph models to fit and simulate models of dynamic networks. Modelling evolutionary analysis of the dynamics of viral. As several pharmaceutical companies are starting large phase iii trials for r5 and x4 drugs, models are needed to predict the coevolutionary and competitive dynamics of virus strains. The quasispecies dynamics on rugged fitness landscape follow a punctuated or steplike pattern in which a population jumps from a low fitness peak to a higher one, stays there for a considerable time before shifting the peak again and eventually reaches the global maximum of the fitness landscape. Hiv is creating natural selection on human populations.
A viral quasispecies is a population structure of viruses with a large numbers of variant genomes related by mutations. Methodology open access modeling of hivaids dynamic. The scientists, led by michael worobey at the university of arizona, relied on evolutionary theory to dig into hivs past. King department of ecology and evolutionary biology, university of. Iranzo j, manrubia sc 2012 evolutionary dynamics of genome segmentation in multipartite viruses. A quasispecies is a large group or cloud of related genotypes that exist in an environment of high mutation rate at stationary state, where a large fraction of offspring are expected to contain one or more mutations relative to the parent. However, the simplest models of virus competition for host resources show the existence of a single dominant strain that grows most rapidly during the initial period of infection and competitively excludes all other virus strains. Pybus1 1department of zoology, university of oxford, oxford, uk.
The earliest hiv cases links to blood sample from central africa around the end of 1950s. Elsevii ecological modelling 92 1996 145153 modeling and managing the evolutionary component of biological systems thomas l. Mutation, competition of uninfected target cells t, free virions v, and infected target cells t dt dt dt. The higher the initial fitness, the less severe must the bottleneck be to avoid fitness losses. Evolutionary dynamics of a multitrait semelparous model 3 traits including color patterns, body shape and size, life history patterns, and behavior 23. A quantitative quasispecies theorybased model of virus. Methodology open access modeling of hivaids dynamic evolution using nonhomogeneous semimarkov process zelalem getahun dessie abstract the purpose of this study is to model the progression of hivaids disease of an individual patient under art followup using nonhomogeneous semimarkov processes. Modelling viral evolution and adaptation springerlink. Evolutionary theory and modeling harvard university.
Hiv and indeed all pathogens are not static infectious particles, but evolving populations. Finally, extensions of quasispecies to nonviral systems are briefly mentioned to emphasize the broad applicability of quasispecies theory. If predicted change in genetic makeup of humans at the coreceptor locus occurs, it will be a major example of human evolution or just evolution. The purpose of this study is to model the progression of hivaids disease of an individual patient under art followup using nonhomogeneous semimarkov processes. Hiv and other retroviruses apart from the evolution of other organisms. Virus evolution during infection of a single individual is a wellknown feature of disease progression in chronic viral diseases.
Our model investigates the action of tumor necrosis factor in aids progression and makes suggestions on better design of haart therapy. To consider the epidemiologic and evolutionary future of hivaids, we developed a mathematical model for the population dynamics of hivaids. As the virus proliferates within an individual, its. During the hiv infection several quasispecies of the virus arise. Philippe lemey, et al hiv evolutionary dynamics 125 hiv evolutionary dynamics within and among hosts philippe lemey1,2, andrew rambaut1 and oliver g. The ribosomal database project rdp provides ribosome related data services to the scientific community. A sample of 1456 patients was taken from a hospital record at amhara referral. Exploratory modeling and simulation of the evolutionary. We have modeled the withinpatient evolutionary process during hiv infection. The rational design of these preventive and treatment measures requires a profound knowledge of the interaction between hiv 1 and its host during the first weeks that follow viral infection i. The model focuses on the patients age as a relevant factor to forecast the transitions among the different levels of seriousness of the disease. A quasispecies is a large group or cloud of related genotypes that exist in an environment of high mutation rate at stationary state, where a large fraction of offspring are expected to contain one or more mutations relative to.
Feb 18, 2014 modeling the evolution and spread of hiv in populations. The human immunodeficiency virus hiv is the causative agent of acquired immunodeficiency syndrome aids, the second most common infectious cause of death globally. Phylogenetic analysis of viral quasispecies by patricia buendia. To consider the epidemiologic and evolutionary future of hiv aids, we developed a mathematical model for the population dynamics of hiv aids. Quasispecies model definition of quasispecies model by. This provides the theoretical and contextual foundation for my genomic interests, and is important to highlight because there have been criticisms of largescale genomic. The virus quasispecies dynamics are explicitly represented by mutations in the combined sequence space of a set of epitopes within the viral genome. Our model is based on those typically employed by demographers and actuaries see reference 4 for our previous publication of it in a mathematical context. During the hiv infection several quasispecies of the virus arise, which are able to use different coreceptors, in particular the ccr5 and cxcr4. Pdf modeling hiv quasispecies evolutionary dynamics. Here, we present a quantitative approach to model the virus evolution under cytotoxic tlymphocyte immune response. A system of three differential equations describes how these quantities change over time.
In this paper we present a distancebased algorithm called minpd to infer evolutionary relationships including recombination in seriallysampled sequence data. Analysis of evolutionary changes in higher primate cytochrome c and cytochrome oxidase. Vincent aerospace and mechanical engineering, university of arizona, tucson, az 85721, usa abstract while differential equations have been commonly used to model the population dynamics of biological systems, it is uncommon for such models to include the evolutionary. Implications and opportunities for hiv prevention research speakers. This high mutation rate of hiv combined with a large effective population size and a short generation time, result in an enormous capacity to generate diversity and to adapt to changes in the host. Modeling the evolution and spread of hiv in populations. A quasispecies model of hiv infection can be derived by the model previously introduced. Society for industrial and applied mathematics summary. Mathematical modelling of the withinhost hiv quasispecies. The evolutionary dynamics of hiv 1 quasispecies and the development of immunodeficiency disease. Vincent aerospace and mechanical engineering, university of arizona, tucson, az 85721, usa abstract while differential equations have been commonly used to model the population dynamics of biological systems, it is uncommon for such models to include the. Results we present a model of hiv early infection which describes the dynamics of r5 quasispecies and a model of hiv late infection which describes the r5 to x4 switch. Modeling of viral and cellular dynamics viral evolution and population genetics these approaches are increasingly applied to viruses other than hiv, so beginning this year, we encourage the submission of abstracts relating to work on other human viruses.
The underlying network organization reveals unique patterns of. We present a model of hiv early infection which describes the dynamics of r5 quasispecies and a model of hiv late infection which describes the r5 to x4 switch. The asymptotic behavior of the quasispecies model is determined by the equilibrium p limt. As several pharmaceutical companies are starting large phase iii trials for r5 and x4 drugs, models are needed to predict the co evolutionary and competitive dynamics of virus strains. In addition, evolution is complicated by the fact that most traits are correlated with a suite of other traits 35.
We welcome submissions on all topics on statistical, mathematical and computational approaches to analyzing the dynamics and evolution of hiv and other human viruses. These quasispecies are able to use different coreceptors, in particular the ccr5 and cxcr4 r5 and x4 phenotypes, respectively. Modules for simulating hiv sti transmission dynamics among men who have sex with men and heterosexual populations, developed as an extension to our general networkbased epidemic modeling platform, epimodel. Despite the remarkable throughput of nextgeneration sequencing technologies, standard techniques are limited by the difficulty in distinguishing sequencing errors. Chapter 1 evolution of hiv virus flashcards quizlet. Modeling hiv quasispecies evolutionary dynamics core. Viral quasispecies constitute reservoirs of genotypic and phenotypic variants drug. Modelling hiv1 evolution rna viruses, such as hiv, have extremely high mutation rates largely attributable to a low fidelity reverse transcriptase. Rna viruses form complex distributions of closely related but nonidentical genomes that are subjected to a continuous process of genetic variation, competition, and selection fig. Despite the fact that financial resources for hiv programs tended to increase between 2000 and 2010, the current scenario has changed and resources have not been increasing at the same rapid rate in more recent years. The first hiv identification was in 1983, and the studies of previously stored blood samples indicate that the hiv entered the u. An important feature of the algorithm is that it does not need the assumption of a molecular clock or an. Complete elimination of human immunodeficiency virus hiv. Evolutionary theory and modeling here i provide background work in mathematical epidemiology and evolutionary theory.
Mathematical modelling of the withinhost hiv quasispecies dynamics in response to antiviral treatment article in russian journal of numerical analysis and mathematical modelling 303 june. Sep 25, 2012 rna viruses form complex distributions of closely related but nonidentical genomes that are subjected to a continuous process of genetic variation, competition, and selection fig. New empirical data and improved models of viral dynamics are clearing up the role played by neutral networks of genotypes 21, by defective and cooperative interactions among viral mutants, by coevolution with immune systems 22, or by changes in host populations 10, to cite but a few examples. Highresolution deep sequencing reveals biodiversity. These socalled viral quasispecies have been described in vivo through the analysis of molecular and biological clones isolated from viral populations, and more recently using ultradeep sequencing techniques. Epidemiology, evolution, and future of the hivaids pandemic. The evolutionary dynamics of hiv1 quasispecies and the development of immunodeficiency disease. Rare hiv1 transmittedfounder lineages identified by deep. Modeling evolutionary dynamics of hiv infection springerlink.
The rational design of these preventive and treatment measures requires a profound knowledge of the interaction between hiv1 and its host during the first weeks that follow viral infection i. If the evolutionary rate of the pathogen is sufficiently high such that the evolutionary and epidemiological timescales are similar, then the evolutionary trees can give insight into the transmission dynamics of the disease pybus et al. This is in contrast to a species, which from an evolutionary perspective is a moreorless st. Modeling hiv quasispecies evolutionary dynamics bmc. Using the chemokine tree topology as conceptual framework for hiv viral speciation, we present a model of viral phenotypic mutations from r5 to x4 strains which reflect hiv late infection dynamics. This provides the theoretical and contextual foundation for my genomic interests, and is important to highlight because there have been criticisms of. Author summary the development of safe, effective, and scalable vaccines and cure strategies to control the hiv1 pandemic is a major public health concern. This and other resistance alleles may be undergoing evolutionary change due to hiv serving as a selective agent on human populations, i. Abstracts are being accepted for the following topics.
Aug 14, 2015 iranzo j, manrubia sc 2012 evolutionary dynamics of genome segmentation in multipartite viruses. Better understanding of hiv epidemic through evolutionary. A viral biorealm page on the family quasispecies theory and novel hiv therapeutics based on lethal mutagenesis. Results we present a model of hiv early infection which describes the dynamics of r5 quasispecies and a model of hiv late infection which describes. The hiv epidemic continues to be a major global health challenges, with more than 33 million people infected worldwide. Therefore, humans are not the nature hosts of either hiv1 or hiv2. Better understanding of hiv epidemic through evolutionary lens.
Mathematical model of hiv superinfection and comparative. Enhancing the accuracy of nextgeneration sequencing for. Quasispecies theory and novel hiv therapeutics based on. By perronfrobenius theorem it follows that there is a unique positive. Quasispecies result from high mutation rates as mutants arise continually and change in relative frequency as viral replication and selection proceeds the theory predicts that a viral quasispecies at a low but evolutionarily neutral and highly connected that is, flat. We adopt a quasispecies description of the process by first hypothesizing the evolution of the virus to be characterized by only one slight changing phenotypic trait, e. Exploratory modeling and simulation of the evolutionary dynamics of singlestranded rna virus populations jaeseung yeom tanya kostovavassilevska peter d. During the earliest evolution on earth, life probably resembled one big genetic jumble.
Author summary the development of safe, effective, and scalable vaccines and cure strategies to control the hiv 1 pandemic is a major public health concern. The basic model of hiv1 dynamics, first introduced by perelson and colleagues in 1995, is a class model considering three variables. The quasispecies model is a description of the process of the darwinian evolution of certain selfreplicating entities within the framework of physical chemistry. The basic model of hiv 1 dynamics, first introduced by perelson and colleagues in 1995, is a class model considering three variables. Modelling hiv 1 evolution rna viruses, such as hiv, have extremely high mutation rates largely attributable to a low fidelity reverse transcriptase. Hivs evolution is particularly rapid because of its high mutation rate up to a million times faster than our own.
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