Phylodynamics analysis of the Human Immunodeficiency Virus type 1 (HIV-1) envelope gene in mother and child pairs (original) (raw)
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PLoS ONE, 2014
Background: Mother-to-child transmission (MTCT) is responsible for most pediatric HIV-1 infections worldwide. It can occur during pregnancy, labor, or breastfeeding. Numerous studies have used coalescent and molecular clock methods to understand the epidemic history of HIV-1, but the timing of vertical transmission has not been studied using these methods. Taking advantage of the constant accumulation of HIV genetic variation over time and using longitudinally sampled viral sequences, we used a coalescent approach to investigate the timing of MTCT.
Journal of Virology, 2003
Although several virologic and immunologic factors associated with an increased risk of perinatal human immunodeficiency virus type 1 (HIV-1) transmission have been described, the mechanism of mother-to-child transmission is still unclear. More specifically, the question of whether selective pressures influence the transmission remains unanswered. The aim of this study was to assess the genetic diversity of the transmitted virus after in utero transmission and after peripartum transmission and to compare the viral heterogeneity in the child with the viral heterogeneity in the mother. To allow a very accurate characterization of the viral heterogeneity in a single sample, limiting-dilution sequencing of a 1,016-bp fragment of the env gene was performed. Thirteen children were tested, including 6 with in utero infections and 7 with peripartum infections. Samples were taken the day after birth and at the ages of 6 and 14 weeks. A homogeneous virus population was seen in six (46.2%) infants, of whom two were infected in utero and four were infected peripartum. A more heterogeneous virus population was detected in seven infants (53.8%), four infected in utero and three infected peripartum. The phylogenetic trees of the mother-child pairs presented a whole range of different tree topologies and showed infection of the child by one or more maternal variants. In conclusion, after HIV-1 transmission from mother to child a heterogeneous virus population was detected in approximately one-half of the children examined. Heterogeneous virus populations were found after peripartum infection as well as after in utero infection. Phylogenetic tree topologies argue against selection processes as the major mechanism driving mother-to-child transmission but support the hypothesis that virus variability is mainly driven by the inoculum level and/or exposure time.
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...
Journal of virology, 1995
In order to elucidate the molecular mechanisms involved in human immunodeficiency virus type 1 (HIV-1) mother-to-child transmission, we have analyzed the genetic variation within the V3 hypervariable domain and flanking regions of the HIV-1 envelope gene in four mother-child transmission pairs. Phylogenetic analysis and amino acid sequence comparison were performed on cell-associated viral sequences derived from maternal samples collected at different time points during pregnancy, after delivery, and from child samples collected from the time of birth until the child was approximately 1 year of age. Heterogeneous sequence populations were observed to be present in all maternal samples collected during pregnancy and postdelivery. In three newborns, viral sequence populations obtained within 2 weeks after birth revealed a high level of V3 sequence variability. In contrast, V3 sequences obtained from the fourth child (diagnosed at the age of 1 month) displayed a more restricted heterog...
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.
Phylogenetic Analysis of HIV-1 Using Dataset of gag gene Sequences
"Objective: Insecure mating between individuals who are both infected with HIV-1 can direct the exposure to their partner's virus and potentially to superinfection. Epidemiological studies of virus help out to scrutinize the genetic divergence, worldwide spread of HIV, and its paths of infection. The infected individuals with HIV-1 hold a vigorously evolving population of closely related genomes. Phylogenetic and genetic analyses have verified a valuable tool to conclude epidemiological links between HIV-1 isolates. Present study was conducted to investigate the epidemiological profiling and molecular diversity of HIV-1 on the bases of gag gene sequences. Methods: Maximum Parsimony, Maximum Likelihood methods were used for the phylogenetic analysis of gag gene sequences. Results: The clades (A,B,C) revealed possible viral spread through phylogenetic approach. HIV-1 gag gene sequence variations among the different strains isolated from different locations resulted in the spread of virus by means of physical carriers. Conclusion: Nucleotide sequences based phylogenetic studies of viral genomes may disclose the mode of spreading and time span as viral genomes keep on changing themselves and their evolutionary rate is the key to calculate the time window of such dispersal."
Genetic diversity and molecular epidemiology of HIV transmission
Future Virology, 2012
The high genetic diversity of HIV is one of its most significant features, as it has consequences in global distribution, vaccine design, therapy success, disease progression, transmissibility and viral load testing. Studying HIV diversity helps to understand its origins, migration patterns, current distribution and transmission events. New advances in sequencing technologies based on the parallel acquisition of data are now used to characterize within-host and population processes in depth. Additionally, we have seen similar advances in statistical methods designed to model the past history of lineages (the phylodynamic framework) to ultimately gain better insights into the evolutionary history of HIV. We can, for example, estimate population size changes, lineage dispersion over geographic areas and epidemiological parameters solely from sequence data. In this article, we review some of the evolutionary approaches used to study transmission patterns and processes in HIV and the in...
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...
Molecular evolution methods to study HIV-1 epidemics
Future Virology
Nucleotide sequences of HIV isolates are obtained routinely to evaluate the presence of resistance mutations to antiretroviral drugs. But, beyond their clinical use, these and other viral sequences include a wealth of information that can be used to better understand and characterize the epidemiology of HIV in relevant populations. In this review, we provide a brief overview of the main methods used to analyze HIV sequences, the data bases where reference sequences can be obtained, and some caveats about the possible applications for public health of these analyses, along with some considerations about their limitations and correct usage to derive robust and reliable conclusions. Executive summary The HIV pandemic affects millions of people worldwide, and there is an increased trend of infections among vulnerable groups, such as MSM. The combination of epidemiological, molecular and evolutionary tools is relevant to depict HIV epidemics. In this way, molecular epidemiology can help to develop detection and prevention campaigns focusing in the most vulnerable populations to HIV infection. This review aims to highlight the most relevant uses of molecular epidemiology, giving an overview of the most common approaches used for understanding HIV epidemics. Consequently, it may be useful for designing correct protocols in HIV epidemiological studies.
Tracing the relationship among HIV-1 sub-subtype F1 strains: a phylodynamic perspective
Memórias do Instituto Oswaldo Cruz
BACKGROUND The human immunodeficiency virus type 1, F1 sub-subtype (HIV-1 F1) circulates in three continents: Africa, Europe, and South America. In Brazil, this sub-subtype co-circulates with subtypes B and C and several recombinant forms, mainly BF1 variants. OBJECTIVES This study aimed to reconstruct the dynamic history of HIV-1 F1 in Brazil. METHODS HIV-1 near full-length genome and pol gene nucleotide sequences available in public databases were assembled in two datasets (POL671 and NFLG53) to cover the largest number of F1 sub-subtype sequences. Phylodynamic and temporal analyses were performed. FINDINGS Two main strains of the F1 sub-subtype are circulating worldwide. The first (F1.I) was found among Brazilian samples (75%) and the second (F1.II) among Romanian (62%) and other European and African isolates. The F1 subtype epidemic in Brazil originated from a single entry into the country around 1970. This ancestral sample is related to samples isolated in European countries (France, Finland, and Belgium), which are possibly of African origin. Moreover, further migration (1998 CI: 1994-2003) of strains from Brazil to Europe (Spain and the UK) was observed. Interestingly, all different recombinant BF patterns found, even those from outside Brazil, present the same F1 lineage (F1.I) as an ancestor, which could be related to the acquisition of adaptive advantages for the recombinant progenies. MAIN CONCLUSIONS These findings are important for the understanding of the origin and dynamics of the F1 sub-subtype and a consequent better and greater understanding of the HIV-1 F1 and BF epidemic that still spreads from Brazil to other countries.