Early-Transmitted Variants and Their Evolution in a HIV-1 Positive Couple: NGS and Phylogenetic Analyses (original) (raw)
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Retrovirology
Background: To combat the pandemic of human immunodeficiency virus 1 (HIV-1), a successful vaccine will need to cope with the variability of transmissible viruses. Human hosts infected with HIV-1 potentially harbour many viral variants but very little is known about viruses that are likely to be transmitted, or even if there are viral characteristics that predict enhanced transmission in vivo. We show for the first time that genetic divergence consistent with a single transmission event in vivo can represent several years of pre-transmission evolution. Results: We describe a highly unusual case consistent with a single donor transmitting highly related but distinct HIV-1 variants to two individuals on the same evening. We confirm that the clustering of viral genetic sequences, present within each recipient, is consistent with the history of a single donor across the viral env, gag and pol genes by maximum likelihood and Bayesian Markov Chain Monte Carlo based phylogenetic analyses. Based on an uncorrelated, lognormal relaxed clock of env gene evolution calibrated with other datasets, the time since the most recent common ancestor is estimated as 2.86 years prior to transmission (95% confidence interval 1.28 to 4.54 years).
AIDS Research and Human Retroviruses, 2012
To characterize phylogenetic relatedness of plasma HIV-1 RNA subtype C env gp120 viral variants capable of establishing an infection following heterosexual and subsequent vertical transmission events a 650-base pair fragment within the C2-V5 subregion was sequenced from four HIV-1-infected families each consisting of biological parent(s), index children (first), and subsequent (second) siblings. None of the family members had received antiretroviral therapy at the time of sample collection. Sequence alignment and analysis were done using Gene Doc, Clustal X, and MEGA software programs. Second siblings' sequences were homogeneous and clustered in a single branch while first siblings' sequences were more heterogeneous, clustering in separate branches, suggestive of more than one donor variants responsible for the infection or evolution from founder variant(s) could have occurred. While the directionality for heterosexual transmission could not be determined, homogeneous viral variants were a unique characteristic of maternal variants as opposed to the more heterogeneous paternal variants. Analysis of families' sequences demonstrated a localized expansion of the subtype C infection. We demonstrated that families' sequences clustered quite closely with other regional HIV-1 subtype C sequences supported by a bootstrap value of 86%, confirming the difficulty of classifying subtype C sequences on a geographic basis. Data are indicative of several mechanisms that may be involved in both vertical and heterosexual transmission. Larger studies are warranted to address the caveats of this study and build on the strengths. Our study could be the beginning of family-based HIV-1 intervention research in Zimbabwe.
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...
Genetic and phylogenetic analyses of HIV1 corroborate the transmission link hypothesis
Journal of Clinical Virology, 2004
Background: Phylogenetic and genetic analyses have proven a valuable tool to infer epidemiological links between human immunodeficiency virus type-1 (HIV-1) isolates. These methods were applied in the present report for studying the genetic relatedness of the viral strains involved in two episodes of suspected HIV-1 transmission. Objectives: Provide any evidence that may help establish or refute the transmission link. Study design: In the first case, a leukemic patient became HIV-1 positive following the transfusion of platelets from a donor who was subsequently found to have tested false HIV-seronegative and to be sexual partner to an infected woman. In the second, a wife claimed to have acquired the infection from her husband who had concealed his infected status. Results and conclusions: The viral pairs detected in each of the suspected transmission cases exhibited common amino acid signatures and low genetic distances and segregated together in phylogenetic trees, thus showing a level of genetic relatedness similar to reference pairs known with certainty to be epidemiologically linked. These findings corroborated the existence of a direct transmission link in both the episodes with a high level of confidence.
Brief Report The Genetic Diversity and Evolution of HIV-1
2016
Abstract: HIV-1 epidemics in Caribbean countries, including Puerto Rico, have been reported to be almost exclusively associated with the subtype B virus (HIV-1B). However, while HIV infections associated with other clades have been only sporadically reported, no organized data exist to accurately assess the prevalence of non-subtype B HIV-1 infection. We analyzed the nucleotide sequence data of the HIV pol gene associated with HIV isolates from Puerto Rican patients. The sequences (n = 945) were obtained from our “HIV Genotyping ” test file, which has been generated over a period of 14 years (2001–2014). REGA subtyping tool found the following subtypes: B (90%), B-like (3%), B/D recombinant (6%), and D/B recombinant (0.6%). Though there were fewer cases, the following subtypes were also found (in the given proportions): A1B (0.3%), BF1 (0.2%), subtype A (01-AE) (0.1%), subtype A (A2) (0.1%), subtype F (12BF) (0.1%), CRF-39 BF-like (0.1%), and others (0.1%). Some of the recombinants ...
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."
h ongoing generation of viral genetic diversity and increasing levels of migration, the global human immunodeficiency virus type 1 (HIV-1) epidemic is becoming increasingly heterogeneous. In this study, we investigate the epidemiological characteristics of 5,675 HIV-1 pol gene sequences sampled from distinct infections in the United Kingdom. These sequences were phylogenetically analyzed in conjunction with 976 complete-genome and 3,201 pol gene reference sequences sampled globally and representing the broad range of HIV-1 genetic diversity, allowing us to estimate the probable geographic origins of the various strains present in the United Kingdom. A statistical analysis of phylogenetic clustering in this data set identified several independent transmission chains within the United Kingdom involving recently introduced strains and indicated that strains more commonly associated with infections acquired heterosexually in East Africa are spreading among men who have sex with men. Coalescent approaches were also used and indicated that the transmission chains that we identify originated in the late 1980s to early 1990s. Similar changes in the epidemiological structuring of HIV epidemics are likely to be taking in place in other industrialized nations with large immigrant populations. The framework implemented here takes advantage of the vast amount of routinely generated HIV-1 sequence data and can provide epidemiological insights not readily obtainable through standard surveillance methods.
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.
The Journal of Infectious Diseases, 2018
BackgroundWe evaluated use of phylogenetic methods to predict the direction of human immunodeficiency virus (HIV) transmission.MethodsFor 33 pairs of HIV-infected patients (hereafter, “index patients”) and their partners who acquired genetically linked HIV infection during the study, samples were collected from partners and index patients close to the time when the partner seroconverted (hereafter, “SC samples”); for 31 pairs, samples collected from the index patient at an earlier time point (hereafter, “early index samples”) were also available. Phylogenies were inferred using env next-generation sequences (1 tree per pair/subtype). The direction of transmission (DoT) predicted from each tree was classified as correct or incorrect on the basis of which sequences (those from the index patient or the partner) were closest to the root. DoT was also assessed using maximum parsimony to infer ancestral node states for 100 bootstrap trees.ResultsDoT was predicted correctly for both single...