Investigating Signs of Recent Evolution in the Pool of Proviral HIV Type 1 DNA during Years of Successful HAART (original) (raw)
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Modeling sequence evolution in acute HIV1 infection
Journal of Theoretical Biology, 2009
We describe a mathematical model and Monte-Carlo (MC) simulation of viral evolution during acute infection. We consider both synchronous and asynchronous processes of viral infection of new target cells. The model enables an assessment of the expected sequence diversity in new HIV-1 infections originating from a single transmitted viral strain, estimation of the most recent common ancestor (MRCA) of the transmitted viral lineage, and estimation of the time to coalesce back to the MRCA. We also calculate the probability of the MRCA being the transmitted virus or an evolved variant. Excluding insertions and deletions, we assume HIV-1 evolves by base substitution without selection pressure during the earliest phase of HIV-1 infection prior to the immune response. Unlike phylogenetic methods that follow a lineage backwards to coalescence, we compare the observed data to a model of the diversification of a viral population forward in time. To illustrate the application of these methods, we provide detailed comparisons of the model and simulations results to 306 envelope sequences obtained from 8 newly infected subjects at a single time point. The data from 6/8 patients were in good agreement with model predictions, and hence compatible with a singlestrain infection evolving under no selection pressure. The diversity of the samples from the other two patients was too great to be explained by the model, suggesting multiple HIV-1-strains were transmitted. The model can also be applied to longitudinal patient data to estimate within-host viral evolutionary parameters.
1995
Phylogenetic analysis was used to study in vivo genetic variation of the V3 region of human immunodeficiency virus type 1 in relation to disease progression in six infants with vertically acquired human immunodeficiency virus type 1 infection. Nucleotide sequences from each infant formed a monophyletic group with similar average branch lengths separating the sets of sequences. In contrast to the star-shaped phylogeny characteristic of interinfant viral evolution, the shape of the phylogeny formed by sequences from the infants who developed AIDS tended to be linear. A computer program, DISTRATE, was written to analyze changes in DNA distance values over time. For the six infants, the rate of divergence from the initial variant was inversely correlated with CD4 cell counts averaged over the first 11 to 15 months of life (r ؍ ؊0.87, P ؍ 0.024). To uncover evolutionary relationships that might be dictated by protein structure and function, tree-building methods were applied to inferred amino acid sequences. Trees constructed from the full-length protein fragment (92 amino acids) showed that viruses from each infant formed a monophyletic group. Unexpectedly, V3 loop protein sequences (35 amino acids) that were found at later time points from the two infants who developed AIDS clustered together. Furthermore, these sequences uniquely shared amino acids that have been shown to confer a T-cell line tropic phenotype. The evolutionary pattern suggests that viruses from these infants with AIDS acquired similar and possibly more virulent phenotypes.
International Letters of Natural Sciences, 2013
HIV-1 or Human Immuno Deficiency Virus-1 is the main causative agent of Acquired Immuno Deficiency Syndrome (AIDS). Human host infected with HIV - 1 extensively harbours many viral variants but very little is known about the difference in pattern[17] of evolution of phylogenetic lineages of HIV-1 non recombinant, normal inter subtype recombinant and main two specific recombinant forms of HIV-1 i.e., Circulating Recombinant Forms (CRFs) and Unique Recombinant Forms (URFs). This study is mainly concerned with study of the difference in evolutionary lineages of non-recombinant and recombinant sequences of HIV-1 genome sequences and identification of geographically rich areas which has reported high degree of HIV-1 occurrence and variety. Total 1550 HIV-1 genome sequences were obtained from HIV Los Alamos Database. The sequences were aligned using MAFFT (Multiple Alignment using Fast Fourier Transform) web server tool. Alignment was carried out using 10 different set of alignment parame...
Journal of Virology, 2014
A population of human immunodeficiency virus (HIV) within a host often descends from a single transmitted/founder virus. The high mutation rate of HIV, coupled with long delays between infection and diagnosis, make isolating and characterizing this strain a challenge. In theory, ancestral reconstruction could be used to recover this strain from sequences sampled in chronic infection; however, the accuracy of phylogenetic techniques in this context is unknown. To evaluate the accuracy of these methods, we applied ancestral reconstruction to a large panel of published longitudinal clonal and/or single-genome-amplification HIV sequence data sets with at least one intrapatient sequence set sampled within 6 months of infection or seroconversion (n ؍ 19,486 sequences, median [interquartile range] ؍ 49 [20 to 86] sequences/set). The consensus of the earliest sequences was used as the best possible estimate of the transmitted/founder. These sequences were compared to ancestral reconstructions from sequences sampled at later time points using both phylogenetic and phylogeny-naive methods. Overall, phylogenetic methods conferred a 16% improvement in reproducing the consensus of early sequences, compared to phylogeny-naive methods. This relative advantage increased with intrapatient sequence diversity (P < 10 ؊5) and the time elapsed between the earliest and subsequent samples (P < 10 ؊5). However, neither approach performed well for reconstructing ancestral indel variation, especially within indel-rich regions of the HIV genome. Although further improvements are needed, our results indicate that phylogenetic methods for ancestral reconstruction significantly outperform phylogeny-naive alternatives, and we identify experimental conditions and study designs that can enhance accuracy of transmitted/founder virus reconstruction. IMPORTANCE When HIV is transmitted into a new host, most of the viruses fail to infect host cells. Consequently, an HIV infection tends to be descended from a single "founder" virus. A priority target for the vaccine research, these transmitted/founder viruses are difficult to isolate since newly infected individuals are often unaware of their status for months or years, by which time the virus population has evolved substantially. Here, we report on the potential use of evolutionary methods to reconstruct the genetic sequence of the transmitted/founder virus from its descendants at later stages of an infection. These methods can recover this ancestral sequence with an overall error rate of about 2.3%-about 15% more information than if we had ignored the evolutionary relationships among viruses. Although there is no substitute for sampling infections at earlier points in time, these methods can provide useful information about the genetic makeup of transmitted/founder HIV.
Change of Positive Selection Pressure on HIV-1 Envelope Gene Inferred by Early and Recent Samples
PLoS ONE, 2011
HIV-1 infection has been on the rise in Japan recently, and the main transmission route has changed from blood transmission in the 1980s to homo-and/or hetero-sexual transmission in the 2000s. The lack of early viral samples with clinical information made it difficult to investigate the possible virological changes over time. In this study, we sequenced 142 full-length env genes collected from 16 Japanese subjects infected with HIV-1 in the 1980s and in the 2000s. We examined the diversity change in sequences and potential adaptive evolution of the virus to the host population. We used a codon-based likelihood method under the branch-site and clade models to detect positive selection operating on the virus. The clade model was extended to account for different positive selection pressures in different viral populations. The result showed that the selection pressure was weaker in the 2000s than in the 1980s, indicating that it might have become easier for the HIV to infect a new host and to develop into AIDS now than 20 years ago and that the HIV may be becoming more virulent in the Japanese population. The study provides useful information on the surveillance of HIV infection and highlights the utility of the extended clade models in analysis of virus populations which may be under different selection pressures.
2006
General introduction / Scope of the thesis | Chapter One arises on a daily basis. This results in a population of closely related but variant viral quasispecies which can be found in an infected individual and explains the propensity of HIV-1 to evade anti-viral pressures such as HAART or immune responses. A great amount of viral variability is observed worldwide 26. There are three main types of HIV-1: M, N and O, which are thought to represent separate introductions from chimpanzees into humans 27. The M-group encompasses more than 99% of the circulating strains and can be further divided into nine principle clades (A,
Widespread Adaptive Evolution in the Human Immunodeficiency Virus Type 1 Genome
Journal of Molecular Evolution, 2003
We investigated variable selective pressures among amino acid sites in HIV-1 genes. Selective pressure at the amino acid level was measured by using the nonsynonymous/synonymous substitution rate ratio (x = d N /d S ). To identify amino acid sites under positive selection with x > 1, we applied maximum likelihood models that allow variable x ratios among sites to analyze genomic sequences of 26 HIV-1 lineages including subtypes A, B, and C. Likelihood ratio tests detected sites under positive selection in each of the major genes in the genome: env, gag, pol, vif, and vpr. Positive selection was also detected in nef, tat, and vpu, although those genes are very small. The majority of positive selection sites is located in gp160. Positive selection was not detected if x was estimated as an average across all sites, indicating the lack of power of the averaging approach. Candidate positive selection sites were mapped onto the available protein tertiary structures and immunogenic epitopes. We measured the physiochemical properties of amino acids and found that those at positive selection sites were more diverse than those at variable sites. Furthermore, amino acid residues at exposed positive selection sites were more physiochemically diverse than at buried positive selection sites. Our results demonstrate genomewide diversifying selection acting on the HIV-1.
Journal of General Virology, 2005
Within human immunodeficiency virus type 1 (HIV-1)-infected patients, there are those who have been infected for more than 10 years with a CD4+ cell count of >500 cells μl−1 and who remain asymptomatic without antiretroviral therapy; these patients are designated long-term non-progressors (LTNPs). In a set of 16 LTNPs, viral dating, DNA viral load, quasispecies heterogeneity and antibody (Ab) titres against gp160 and β 2 microglobulin (β 2m) were determined. Plasma viral RNA and CD4+ and CD8+ T-cell numbers were estimated in more than three samples per patient. Host genetic characteristics, such as Δ32-CCR5 genotype and human leukocyte antigen (HLA) genotype and supertypes, and clinical–epidemiological factors were evaluated. Dating of global populations and of DNA and RNA viral quasispecies identified two subsets of patients: one displaying only ancestral sequences and the other displaying predominantly modern sequences. The ancestral patients displayed a significant reduction i...
The Journal of general virology, 2001
In order to study the evolution in vivo of human immunodeficiency virus type 1 (HIV-1) in patients with normal clinical evolution, six individuals were selected from a group of 46 patients followed for 1 to 4 years. Patients were selected not by clinical progression characteristics but on the basis of virus genetic variability, as analysed by heteroduplex mobility assay and RNase A mismatch cleavage method. Two patients displayed a homogeneous virus population, two showed very heterogeneous quasispecies and two presented two distinct variants within the virus population. Virus quasispecies were studied by nucleotide sequencing of the C2-fusion domain of the env gene. Virus evolution was approached by analysing the distribution of genetic distances, calculation of divergence and heterogeneity as well as the K(a)/K(s) ratio and by the construction of the phylogenetic trees. Three patients displayed the same tree topology, characterized by the presence of independent clades supported b...
Quantifying Differences in the Tempo of Human Immunodeficiency Virus Type 1 Subtype Evolution
Journal of Virology, 2009
Human immunodeficiency virus type 1 (HIV-1) genetic diversity, due to its high evolutionary rate, has long been identified as a main cause of problems in the development of an efficient HIV-1 vaccine. However, little is known about differences in evolutionary rate between different subtypes. In this study, we collected representative samples of the main epidemic subtypes and circulating recombinant forms (CRFs), namely, sub-subtype A1, subtypes B, C, D, and G, and CRFs 01_AE and 02_AG. We analyzed separate data sets for pol and env. We performed a Bayesian Markov chain Monte Carlo relaxed-clock phylogenetic analysis and applied a codon model to the resulting phylogenetic trees to estimate nonsynonymous (dN) and synonymous (dS) rates along each and every branch. We found important differences in the evolutionary rates of the different subtypes. These are due to differences not only in the dN rate but also in the dS rate, varying in roughly similar ways, indicating that these differen...