RESUMO
We introduce a conceptual bridge between the previously unlinked fields of phylogenetics and mathematical spatial ecology, which enables the spatial parameters of an emerging epidemic to be directly estimated from sampled pathogen genome sequences. By using phylogenetic history to correct for spatial autocorrelation, we illustrate how a fundamental spatial variable, the diffusion coefficient, can be estimated using robust nonparametric statistics, and how heterogeneity in dispersal can be readily quantified. We apply this framework to the spread of the West Nile virus across North America, an important recent instance of spatial invasion by an emerging infectious disease. We demonstrate that the dispersal of West Nile virus is greater and far more variable than previously measured, such that its dissemination was critically determined by rare, long-range movements that are unlikely to be discerned during field observations. Our results indicate that, by ignoring this heterogeneity, previous models of the epidemic have substantially overestimated its basic reproductive number. More generally, our approach demonstrates that easily obtainable genetic data can be used to measure the spatial dynamics of natural populations that are otherwise difficult or costly to quantify.
Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Demografia , Evolução Molecular , Modelos Biológicos , Filogenia , Febre do Nilo Ocidental/epidemiologia , Vírus do Nilo Ocidental/genética , Sequência de Bases , Teorema de Bayes , Doenças Transmissíveis Emergentes/transmissão , Humanos , Modelos Genéticos , Dados de Sequência Molecular , América do Norte/epidemiologia , Filogeografia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Febre do Nilo Ocidental/transmissãoRESUMO
Chronic hepatitis C virus (HCV) infection can lead to liver cirrhosis in up to 20% of individuals, often requiring liver transplantation. Although the new liver is known to be rapidly reinfected, the dynamics and source of the reinfecting virus(es) are unclear, resulting in some confusion concerning the relationship between clinical outcome and viral characteristics. To clarify the dynamics of liver reinfection, longitudinal serum viral samples from 10 transplant patients were studied. Part of the E1/E2 region was sequenced, and advanced phylogenetic analysis methods were used in a multiparameter analysis to determine the history and ancestry of reinfecting lineages. Our results demonstrated the complexity of HCV evolutionary dynamics after liver transplantation, in which a large diverse population of viruses is transmitted and maintained for months to years. As many as 30 independent lineages in a single patient were found to reinfect the new liver. Several later posttransplant lineages were more closely related to older pretransplant viruses than to viruses detected immediately after transplantation. Although our data are consistent with a number of interpretations, the persistence of high viral genetic variation over long periods of time requires an active mechanism. We discuss possible scenarios, including frequency-dependent selection or variation in selective pressure among viral subpopulations, i.e., the population structure. The latter hypothesis, if correct, could have relevance to the success of newer direct-acting antiviral therapies.
Assuntos
Hepacivirus/isolamento & purificação , Hepatite C Crônica/cirurgia , Hepatite C Crônica/virologia , Transplante de Fígado , Carga Viral , Adulto , Idoso , Análise por Conglomerados , Variação Genética , Hepacivirus/classificação , Hepacivirus/genética , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Proteínas do Envelope Viral/genéticaRESUMO
Staphylococcus aureus is a common cause of infections that has undergone rapid global spread over recent decades. Formal phylogeographic methods have not yet been applied to the molecular epidemiology of bacterial pathogens because the limited genetic diversity of data sets based on individual genes usually results in poor phylogenetic resolution. Here, we investigated a whole-genome single nucleotide polymorphism (SNP) data set of health care-associated Methicillin-resistant S. aureus sequence type 239 (HA-MRSA ST239) strains, which we analyzed using Markov spatial models that incorporate geographical sampling distributions. The reconstructed timescale indicated a temporal origin of this strain shortly after the introduction of Methicillin, followed by global pandemic spread. The estimate of the temporal origin was robust to the molecular clock, coalescent prior, full/intergenic/synonymous SNP inclusion, and correction for excluded invariant site patterns. Finally, phylogeographic analyses statistically supported the role of human movement in the global dissemination of HA-MRSA ST239, although it was unable to conclusively resolve the location of the root. This study demonstrates that bacterial genomes can indeed contain sufficient evolutionary information to elucidate the temporal and spatial dynamics of transmission. Future applications of this approach to other bacterial strains may provide valuable epidemiological insights that may justify the cost of genome-wide typing.
Assuntos
Evolução Molecular , Estudo de Associação Genômica Ampla/métodos , Staphylococcus aureus Resistente à Meticilina/genética , Teorema de Bayes , Doenças Transmissíveis/microbiologia , Humanos , Funções Verossimilhança , Cadeias de Markov , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Modelos Genéticos , Filogenia , Filogeografia , Infecções Estafilocócicas/microbiologiaRESUMO
Infection of CD8-depleted rhesus macaques with the genetically heterogeneous simian immunodeficiency virus (SIV)mac251 viral swarm provides a rapid-disease model for simian acquired immune deficiency syndrome and SIV-encephalitis (SIVE). The objective was to evaluate how the diversity of the swarm influences the initial seeding of the infection that may potentially affect disease progression. Plasma, lymphoid and non-lymphoid (brain and lung) tissues were collected from two infected macaques euthanized at 21 days post-infection (p.i.), as well as longitudinal specimens and post-mortem tissues from four macaques followed throughout the infection. About 1300 gp120 viral sequences were obtained from the infecting SIVmac251 swarm and the macaques longitudinal and post-mortem samples. Phylogenetic and amino acid signature pattern analyses were carried out to assess frequency, transmission dynamics and persistence of specific viral clusters. Although no significant reduction in viral heterogeneity was found early in infection (21 days p.i.), transmission and replication of SIV variants was not entirely random. In particular, two distinct motifs under-represented (<4 %) in the infecting swarm were found at high frequencies (up to 14 %) in all six macaques as early as 21 days p.i. Moreover, a macrophage tropic variant not detected in the viral swarm (<0.3 %) was present at high frequency (29-100 %) in sequences derived from the brain of two macaques with meningitis or severe SIVE. This study demonstrates the highly efficient transmission and persistence in vivo of multiple low frequency SIVmac251 founder variants, characterized by specific gp120 motifs that may be linked to pathogenesis in the rapid-disease model of neuroAIDS.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Encefalite Viral/virologia , Síndrome de Imunodeficiência Adquirida dos Símios/transmissão , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/isolamento & purificação , Vírus da Imunodeficiência Símia/patogenicidade , Animais , Encéfalo/virologia , Análise por Conglomerados , Modelos Animais de Doenças , Pulmão/virologia , Depleção Linfocítica , Macaca mulatta , Dados de Sequência Molecular , Filogenia , Plasma/virologia , Polimorfismo Genético , RNA Viral/genética , Análise de Sequência de DNA , Síndrome de Imunodeficiência Adquirida dos Símios/complicaçõesRESUMO
The rate of new emerging infectious diseases entering the human population has increased over the past century, with pathogens originating from animals or from products of animal origin accounting for the vast majority. Primary risk factors for the emergence and spread of emerging zoonoses include expansion and intensification of animal agriculture and long-distance live animal transport, live animal markets, bushmeat consumption and habitat destruction. Developing effective control strategies is contingent upon the ability to test causative hypotheses of disease transmission within a statistical framework. Broadly speaking, molecular phylogeography offers a framework in which specific hypotheses regarding pathogen gene flow and dispersal within an ecological context can be compared. A number of different methods has been developed for this application. Here, our intent is firstly to discuss the application of a wide variety of statistically based methods (including Bayesian reconstruction, network parsimony analysis and regression) to specific viruses (influenza, salmon anaemia virus, foot and mouth disease and Rift Valley Fever) that have been associated with animal farming/movements; and secondly to place them in the larger framework of the threat of potential zoonotic events as well as the economic and biosecurity implications of pathogen outbreaks among our animal food sources.
Assuntos
Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/virologia , Filogeografia , Viroses/epidemiologia , Viroses/virologia , Animais , Doenças Transmissíveis/transmissão , Reservatórios de Doenças , Humanos , Viroses/prevenção & controle , Viroses/transmissão , Zoonoses/epidemiologia , Zoonoses/transmissão , Zoonoses/virologiaRESUMO
BACKGROUND: Little is known about HIV-1 subtype distribution in Morocco. Some data suggest an emergence of new HIV subtypes. We conducted phylogenetic analysis on a nationally representative sample of 60 HIV-1 viral specimens collected during 2004-2005 through the Morocco national HIV sentinel surveillance survey. RESULTS: While subtype B is still the most prevalent, 23.3% of samples represented non-B subtypes, the majority of which were classified as CRF02_AG (15%). Molecular clock analysis confirmed that the initial introduction of HIV-1B in Morocco probably came from Europe in the early 1980s. In contrast, the CRF02_AG strain appeared to be introduced from sub-Saharan Africa in two separate events in the 1990s. CONCLUSIONS: Subtype CRF02_AG has been emerging in Morocco since the 1990s. More information about the factors introducing HIV subtype-specific transmission will inform the prevention strategy in the region.
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BACKGROUND: Hepatitis C virus (HCV) is a rapidly-evolving RNA virus that establishes chronic infections in humans. Despite the virus' public health importance and a wealth of sequence data, basic aspects of HCV molecular evolution remain poorly understood. Here we investigate three sets of whole HCV genomes in order to directly compare the evolution of whole HCV genomes at different biological levels: within- and among-hosts. We use a powerful Bayesian inference framework that incorporates both among-lineage rate heterogeneity and phylogenetic uncertainty into estimates of evolutionary parameters. RESULTS: Most of the HCV genome evolves at ~0.001 substitutions/site/year, a rate typical of RNA viruses. The antigenically-important E1/E2 genome region evolves particularly quickly, with correspondingly high rates of positive selection, as inferred using two related measures. Crucially, in this region an exceptionally higher rate was observed for within-host evolution compared to among-host evolution. Conversely, higher rates of evolution were seen among-hosts for functionally relevant parts of the NS5A gene. There was also evidence for slightly higher evolutionary rate for HCV subtype 1a compared to subtype 1b. CONCLUSIONS: Using new statistical methods and comparable whole genome datasets we have quantified, for the first time, the variation in HCV evolutionary dynamics at different scales of organisation. This confirms that differences in molecular evolution between biological scales are not restricted to HIV and may represent a common feature of chronic RNA viral infection. We conclude that the elevated rate observed in the E1/E2 region during within-host evolution more likely results from the reversion of host-specific adaptations (resulting in slower long-term among-host evolution) than from the preferential transmission of slowly-evolving lineages.
Assuntos
Hepacivirus/genética , Hepatite C/virologia , Teorema de Bayes , Feminino , Genoma Viral , Hepacivirus/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Modelos Genéticos , FilogeniaRESUMO
Human immunodeficiency virus type 1 subtype C (HIV-1C) represents 30-65% of HIV infections in southern Brazil, and isolated cases of HIV-1C infection have also been reported in Argentina, Uruguay, Paraguay and Venezuela. Phylogenetic studies have suggested that the Brazilian subtype C epidemic was initiated by the introduction of closely related strains. Nevertheless, because of sampling limitations, the point of entry and the timing of subtype C introduction into Brazil, as well as the origin of the founder lineage, remain controversial. The present study investigated the origin, spread and phylogeography of HIV-1C in South America. Phylogenetic analysis showed a well-supported monophyletic clade including all available strains from Brazil, Uruguay and Argentina. Only one lineage from Venezuela was unrelated to the epidemic involving the other three countries. Molecular clock and likelihood mapping analysis showed that HIV-1C introduction in Brazil dated back to the period 1960-1970, much earlier than previously thought, and was followed by a nearly simultaneous star-like outburst of viral lineages, indicating a subsequent rapid spread. Phylogeographic patterns suggested Paraná or Rio Grande do Sul as the possible entrance points of subtype C and an asymmetrical gene flow from Paraná to Sao Paulo, Santa Catarina and Rio Grande do Sul, as well as from Rio Grande do Sul to Sao Paulo fostered by the strong inter-connectivity between population centres in southern Brazil. The study illustrates how coupling phylogeography inference with geographical information system data is critical to understand the origin and dissemination of viral pathogens and potentially predict their future spread.
Assuntos
Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , Filogeografia/métodos , Epidemias , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Dados de Sequência Molecular , América do Sul/epidemiologiaRESUMO
BACKGROUND: Ethanol is metabolized by 2 rate-limiting reactions: alcohol dehydrogenases (ADH) convert ethanol to acetaldehyde that is subsequently metabolized to acetate by aldehyde dehydrogenases (ALDH). Approximately 50% of East Asians have genetic variants that significantly impair this pathway and influence alcohol dependence (AD) vulnerability. We investigated whether variation in alcohol metabolism genes might alter the AD risk in four non-East Asian populations by performing systematic haplotype association analyses to maximize the chances of capturing functional variation. METHODS: Haplotype-tagging SNPs were genotyped using the Illumina GoldenGate platform. Genotypes were available for 40 SNPs across the ADH genes cluster and 24 SNPs across the two ALDH genes in four diverse samples that included cases (lifetime AD) and controls (no Axis 1 disorders). The case control sample sizes were the following: Finnish Caucasians: 232, 194; African Americans: 267, 422; Plains American Indians: 226, 110; and Southwestern American (SW) Indians: 317, 72. RESULTS: In all four populations, as well as HapMap populations, 5 haplotype blocks were identified across the ADH gene cluster: (i) ADH5-ADH4; (ii) ADH6-ADH1A-ADH1B; (iii) ADH1C; (iv) intergenic; (v) ADH7. The ALDH1A1 gene was defined by 4 blocks and ALDH2 by 1 block. No haplotype or SNP association results were significant after correction for multiple comparisons; however, several results, particularly for ALDH1A1 and ADH4, replicated earlier findings. There was an ALDH1A1 block 1 and 2 (extending from intron 5 to the 3' UTR) yin yang haplotype (haplotypes that have opposite allelic configuration) association with AD in the Finns driven by SNPs rs3764435 and rs2303317, respectively, and an ALDH1A1 block 3 (including the promoter region) yin yang haplotype association in SW Indians driven by 5 SNPs, all in allelic identity. The ADH4 SNP rs3762894 was associated with AD in Plains Indians. CONCLUSIONS: The systematic evaluation of alcohol-metabolizing genes in four non-East Asian populations has shown only modest associations with AD, largely for ALDH1A1 and ADH4. A concentration of signals for AD with ALDH1A1 yin yang haplotypes in several populations warrants further study.
Assuntos
Álcool Desidrogenase/genética , Alcoolismo/genética , Etanol/metabolismo , Haplótipos , Isoenzimas/genética , Polimorfismo de Nucleotídeo Único , Retinal Desidrogenase/genética , Negro ou Afro-Americano/genética , Família Aldeído Desidrogenase 1 , Alelos , Feminino , Genótipo , Humanos , Indígenas Norte-Americanos/genética , Masculino , População Branca/genéticaRESUMO
BACKGROUND: Human T-lymphotropic virus type 4 (HTLV-4) is a new deltaretrovirus recently identified in a primate hunter in Cameroon. Limited sequence analysis previously showed that HTLV-4 may be distinct from HTLV-1, HTLV-2, and HTLV-3, and their simian counterparts, STLV-1, STLV-2, and STLV-3, respectively. Analysis of full-length genomes can provide basic information on the evolutionary history and replication and pathogenic potential of new viruses. RESULTS: We report here the first complete HTLV-4 sequence obtained by PCR-based genome walking using uncultured peripheral blood lymphocyte DNA from an HTLV-4-infected person. The HTLV-4(1863LE) genome is 8791-bp long and is equidistant from HTLV-1, HTLV-2, and HTLV-3 sharing only 62-71% nucleotide identity. HTLV-4 has a prototypic genomic structure with all enzymatic, regulatory, and structural proteins preserved. Like STLV-2, STLV-3, and HTLV-3, HTLV-4 is missing a third 21-bp transcription element found in the long terminal repeats of HTLV-1 and HTLV-2 but instead contains unique c-Myb and pre B-cell leukemic transcription factor binding sites. Like HTLV-2, the PDZ motif important for cellular signal transduction and transformation in HTLV-1 and HTLV-3 is missing in the C-terminus of the HTLV-4 Tax protein. A basic leucine zipper (b-ZIP) region located in the antisense strand of HTLV-1 and believed to play a role in viral replication and oncogenesis, was also found in the complementary strand of HTLV-4. Detailed phylogenetic analysis shows that HTLV-4 is clearly a monophyletic viral group. Dating using a relaxed molecular clock inferred that the most recent common ancestor of HTLV-4 and HTLV-2/STLV-2 occurred 49,800 to 378,000 years ago making this the oldest known PTLV lineage. Interestingly, this period coincides with the emergence of Homo sapiens sapiens during the Middle Pleistocene suggesting that early humans may have been susceptible hosts for the ancestral HTLV-4. CONCLUSION: The inferred ancient origin of HTLV-4 coinciding with the appearance of Homo sapiens, the propensity of STLVs to cross-species into humans, the fact that HTLV-1 and -2 spread globally following migrations of ancient populations, all suggest that HTLV-4 may be prevalent. Expanded surveillance and clinical studies are needed to better define the epidemiology and public health importance of HTLV-4 infection.
Assuntos
Deltaretrovirus/genética , Evolução Molecular , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular , Deltaretrovirus/química , Deltaretrovirus/classificação , Genoma Viral , Humanos , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de Aminoácidos , Sequências Repetidas Terminais , Proteínas Virais/química , Proteínas Virais/genéticaRESUMO
Since recombination leads to the generation of mosaic genomes that violate the assumption of traditional phylogenetic methods that sequence evolution can be accurately described by a single tree, results and conclusions based on phylogenetic analysis of data sets including recombinant sequences can be severely misleading. Many methods are able to adequately detect recombination between diverse sequences, for example between different HIV-1 subtypes. More problematic is the identification of recombinants among closely related sequences such as a viral population within a host. We describe a simple algorithmic procedure that enables detection of intra-host recombinants based on split-decomposition networks and a robust statistical test for recombination. By applying this algorithm to several published HIV-1 data sets we conclude that intra-host recombination was significantly underestimated in previous studies and that up to one-third of the env sequences longitudinally sampled from a given subject can be of recombinant origin. The results show that our procedure can be a valuable exploratory tool for detection of recombinant sequences before phylogenetic analysis, and also suggest that HIV-1 recombination in vivo is far more frequent and significant than previously thought.
Assuntos
Algoritmos , HIV-1/genética , Modelos Genéticos , Filogenia , Recombinação Genética , DNA Viral/genética , Evolução Molecular , Genética Populacional , Infecções por HIV/genética , Infecções por HIV/virologia , Humanos , Alinhamento de Sequência , Análise de Sequência de DNA , Estatísticas não ParamétricasRESUMO
Characterizing the impact of HIV transmission routes on viral genetic diversity can improve the understanding of the mechanisms of virus evolution and adaptation. HIV vertical transmission can occur in utero, during delivery, or while breastfeeding. The present study investigated the phylodynamics of the HIV-1 env gene in mother-to-child transmission by analyzing one chronically infected pair from Brazil and three acutely infected pairs from Zambia, with three to five time points. Sequences from 25 clones from each sample were obtained and aligned using Clustal X. ML trees were constructed in PhyML using the best evolutionary model. Bayesian analyses testing the relaxed and strict molecular clock were performed using BEAST and a Bayesian Skyline Plot (BSP) was construed. The genetic variability of previously described epitopes was investigated and compared between each individual time point and between mother and child sequences. The relaxed molecular clock was the best-fitted model for all datasets. The tree topologies did not show differentiation in the evolutionary dynamics of the virus circulating in the mother from the viral population in the child. In the BSP, the effective population size was more constant in time in the chronically infected patients while in the acute patients it was possible to detect bottlenecks. The genetic variability within viral epitopes recognized by the human immune system was considerably higher among the chronically infected pair in comparison with acutely infected pairs. These results contribute to a better understanding of HIV-1 evolutionary dynamics in mother-to-child transmission.
Assuntos
Genes env , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/genética , Adulto , Teorema de Bayes , Brasil , Criança , Pré-Escolar , Evolução Molecular , Feminino , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas , Filogenia , Alinhamento de Sequência , Análise de Sequência de DNA , ZâmbiaRESUMO
Reconstructing the transmission history of infectious diseases in the absence of medical or epidemiological records often relies on the evolutionary analysis of pathogen genetic sequences. The precision of evolutionary estimates of epidemic history can be increased by the inclusion of sequences derived from 'archived' samples that are genetically distinct from contemporary strains. Historical sequences are especially valuable for viral pathogens that circulated for many years before being formally identified, including HIV and the hepatitis C virus (HCV). However, surprisingly few HCV isolates sampled before discovery of the virus in 1989 are currently available. Here, we report and analyse two HCV subgenomic sequences obtained from infected individuals in 1953, which represent the oldest genetic evidence of HCV infection. The pairwise genetic diversity between the two sequences indicates a substantial period of HCV transmission prior to the 1950s, and their inclusion in evolutionary analyses provides new estimates of the common ancestor of HCV in the USA. To explore and validate the evolutionary information provided by these sequences, we used a new phylogenetic molecular clock method to estimate the date of sampling of the archived strains, plus the dates of four more contemporary reference genomes. Despite the short fragments available, we conclude that the archived sequences are consistent with a proposed sampling date of 1953, although statistical uncertainty is large. Our cross-validation analyses suggest that the bias and low statistical power observed here likely arise from a combination of high evolutionary rate heterogeneity and an unstructured, star-like phylogeny. We expect that attempts to date other historical viruses under similar circumstances will meet similar problems.
Assuntos
Evolução Molecular , Genoma Viral , Hepacivirus/genética , Hepatite C/virologia , Sequência de Bases , Variação Genética , Hepatite C/epidemiologia , Humanos , Dados de Sequência Molecular , Filogenia , Alinhamento de Sequência , Estados Unidos/epidemiologiaRESUMO
In approximately 70% of individuals infected with HIV-1 subtype B, the virus switches coreceptor use from exclusively CCR5 use (R5 virus) to either inclusion of or exclusively CXCR4 use (X4 virus) during infection. This switch is associated with an accelerated loss of CD4(+) T-cells and a faster progression to AIDS. Despite intensive research, the mechanisms responsible for coreceptor switch remains elusive. In the present study, we investigated associations between viral evolutionary rate and selection pressure versus viral coreceptor use and rate of disease progression in eight patients with longitudinally sampled HIV-1 env V1-V3 sequences. By employing a Bayesian hierarchical phylogenetic model, we found that the HIV-1 evolutionary rate was more strongly associated with coreceptor switch than with rate of disease progression in terms of CD4(+)T-cell decline. Phylogenetic analyses showed that X4 variants evolved from R5 populations. In addition, coreceptor switch was associated with higher evolutionary rates on both the synonymous and non-synonymous substitution level, but not with dN/dS ratio rates. Our findings suggest that X4 viruses evolved from pre-existing R5 viral populations and that the evolution of coreceptor switch is governed by high replication rates rather than by selective pressure. Furthermore, the association of viral evolutionary rate was more strongly associated with coreceptor switch than disease progression. This adds to the understanding of the complex virus-host interplay that influences the evolutionary dynamics of HIV-1 coreceptor use.
Assuntos
Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/genética , HIV-1/fisiologia , Receptores CCR5/metabolismo , Receptores CXCR4/metabolismo , Teorema de Bayes , Evolução Molecular , HIV-1/classificação , HIV-1/patogenicidade , Interações Hospedeiro-Patógeno , Humanos , Filogenia , Tropismo ViralRESUMO
OBJECTIVE/DESIGN: The global spread of HIV-1 main group (group M) has resulted in differential distributions of subtypes and recombinants, with the greatest diversity being found in sub-Saharan Africa. The explanations for the current subtype distribution patterns are likely multifactorial, but the promotion of human migrations and movements through transportation link availability and quality, summarized through 'accessibility', have been consistently cited as strong drivers. We sought to address the question of whether accessibility has been a significant factor in HIV-1 spread across mainland Africa through spatial analyses of molecular epidemiology, transport network and land cover data. METHODS: The distribution of HIV-1 subtypes and recombinants in sub-Saharan Africa for the period 1998-2008 was mapped using molecular epidemiology data at a finer level of detail than ever before. Moreover, hypotheses on the role of distance, road network structure and accessibility in explaining the patterns seen were tested using spatial datasets representing African transport infrastructure, land cover and an accessibility model of landscape travel speed. RESULTS: Coherent spatial patterns in HIV-1 subtype distributions across the continent exist, and a substantial proportion of the variance in the distribution and diversity pattern seen can be explained by variations in regional spatial accessibility. CONCLUSION: The study confirms quantitatively the influence of transport infrastructure on HIV-1 spread within Africa, presents an approach for examining potential future impacts of road development projects and, more generally, highlights the importance of accessibility in the spread of communicable diseases.
Assuntos
Farmacorresistência Viral , Emigração e Imigração/estatística & dados numéricos , Infecções por HIV/epidemiologia , HIV-1/genética , Síndrome da Imunodeficiência Adquirida/epidemiologia , África Subsaariana/epidemiologia , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/virologia , Surtos de Doenças , Evolução Molecular , Feminino , Infecções por HIV/prevenção & controle , HIV-1/patogenicidade , Humanos , Masculino , Filogeografia , Crescimento Demográfico , Recombinação Genética , ViagemRESUMO
Serially-sampled nucleotide sequences can be used to infer demographic history of evolving viral populations. The shape of a phylogenetic tree often reflects the interplay between evolutionary and ecological processes. Several approaches exist to analyze the topology and traits of a phylogenetic tree, by means of tree balance, branching patterns and comparative properties. The temporal clustering (TC) statistic is a new topological measure, based on ancestral character reconstruction, which characterizes the temporal structure of a phylogeny. Here, PhyloTempo is the first implementation of the TC in the R language, integrating several other topological measures in a user-friendly graphical framework. The comparison of the TC statistic with other measures provides multifaceted insights on the dynamic processes shaping the evolution of pathogenic viruses. The features and applicability of PhyloTempo were tested on serially-sampled intra-host human and simian immunodeficiency virus population data sets. PhyloTempo is distributed under the GNU general public license at https://sourceforge.net/projects/phylotempo/.
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Brain infection by the human immunodeficiency virus type 1 (HIV-1) has been investigated in many reports with a variety of conclusions concerning the time of entry and degree of viral compartmentalization. To address these diverse findings, we sequenced HIV-1 gp120 clones from a wide range of brain, peripheral and meningeal tissues from five patients who died from several HIV-1 associated disease pathologies. High-resolution phylogenetic analysis confirmed previous studies that showed a significant degree of compartmentalization in brain and peripheral tissue subpopulations. Some intermixing between the HIV-1 subpopulations was evident, especially in patients that died from pathologies other than HIV-associated dementia. Interestingly, the major tissue harboring virus from both the brain and peripheral tissues was the meninges. These results show that (1) HIV-1 is clearly capable of migrating out of the brain, (2) the meninges are the most likely primary transport tissues, and (3) infected brain macrophages comprise an important HIV reservoir during highly active antiretroviral therapy.
Assuntos
Encéfalo/virologia , HIV-1/fisiologia , Meninges/virologia , HIV-1/classificação , HIV-1/genética , Humanos , FilogeniaRESUMO
DESIGN: the origin and evolution of HIV-1 in breast milk is unclear, despite the continuing significance of this tissue as a transmitting compartment. To elucidate the evolutionary trajectory of viral populations in a transient mucosal compartment, longitudinal sequences of the envelope glycoprotein (gp120) region from plasma and breast milk spanning the first year after delivery were analyzed in six women infected by HIV-1 subtype C. METHODS: multiple phylogenetic algorithms were used to elucidate the evolutionary history and spatial structure of virus populations between tissues. RESULTS: overall persistent mixing of viral sequences between plasma and breast milk indicated that breast milk is not a distinct genetic viral compartment. Unexpectedly, longitudinal phylogenies showed multiple lineages defined by long branches that included virus from both the breast milk and the plasma. Plasma was unlikely the anatomical origin of the most recent common ancestor (MRCA) in at least three of the patients, although in other women, the temporal origin of the MRCA of the viral populations following delivery occurred well before the onset of breast milk production. CONCLUSIONS: these findings suggest that during pregnancy/lactation, a viral variant distinct from the plasma virus initially seeds the breast milk, followed by subsequent gene flow between the plasma and breast milk tissues. This study indicates the potential for reactivation or reintroduction of distinct lineages during major immunological disruptions during the course of natural infection.