Dataset Information

Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

ABSTRACT: Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission shapes the nascent founder viral genome. Analysis of 74 acute and early HIV-1 infected subjects revealed that 83% of men who have sex with men (MSM) exhibit a single founder virus, levels similar to those previously observed in heterosexual (HSX) transmission. In a metadata analysis of a total of 354 subjects, including HSX, MSM and injecting drug users (IDU), we also observed no significant differences in the frequency of single founder virus infections between HSX and MSM transmissions. However, comparison of HIV-1 envelope sequences revealed that HSX founder viruses exhibited a greater number of codon sites under positive selection, as well as stronger transmission indices possibly reflective of higher fitness variants. Moreover, specific genetic "signatures" within MSM and HSX founder viruses were identified, with single polymorphisms within gp41 enriched among HSX viruses while more complex patterns, including clustered polymorphisms surrounding the CD4 binding site, were enriched in MSM viruses. While our findings do not support an influence of the mode of sexual transmission on the number of founder viruses, they do demonstrate that there are marked differences in the selection bottleneck that can significantly shape their genetic composition. This study illustrates the complex dynamics of the transmission bottleneck and reveals that distinct genetic bottleneck processes exist dependent upon the mode of HIV-1 transmission.

SUBMITTER: Tully DC

PROVIDER: S-EPMC4862634 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

Tully Damien C DC Ogilvie Colin B CB Batorsky Rebecca E RE Bean David J DJ Power Karen A KA Ghebremichael Musie M Bedard Hunter E HE Gladden Adrianne D AD Seese Aaron M AM Amero Molly A MA Lane Kimberly K McGrath Graham G Bazner Suzane B SB Tinsley Jake J Lennon Niall J NJ Henn Matthew R MR Brumme Zabrina L ZL Norris Philip J PJ Rosenberg Eric S ES Mayer Kenneth H KH Jessen Heiko H Kosakovsky Pond Sergei L SL Walker Bruce D BD Altfeld Marcus M Carlson Jonathan M JM Allen Todd M TM

PLoS pathogens 20160510 5

Due to the stringent population bottleneck that occurs during sexual HIV-1 transmission, systemic infection is typically established by a limited number of founder viruses. Elucidation of the precise forces influencing the selection of founder viruses may reveal key vulnerabilities that could aid in the development of a vaccine or other clinical interventions. Here, we utilize deep sequencing data and apply a genetic distance-based method to investigate whether the mode of sexual transmission sh ...[more]

PMID: 27163788

Similar Datasets

Project description:Transmission of multiple founder variants has been associated with faster HIV disease progression. Many studies have attempted to determine the number of founder variants, mainly by analysis of sequence diversity and/or tree topology from acutely HIV-infected individuals. We hypothesized that adding sequence data collected from source partners might improve resolution and characterization of transmission events. Blood plasma samples were collected from both the source and recipient in thirty epidemiologically- and phylogenetically linked transmission pairs. All were men who have sex with men, sampled on average 70 days (range 11-170) after the recipient's estimated date of infection. Next generation sequencing (454 FLX, Roche) of HIV-1 env (C2-V3) was performed for all samples. Inspection of sequence alignments, highlighter plots, phylogenetic tree topologies and sequence diversity were used to determine the multiplicity of founder viruses with and without the inclusion of source data. Using only recipient sequence data, we were able to resolve multiplicity in twenty-six of the thirty transmission pairs (87 percent). Among them, five presented with a high viral diversity at baseline (>0.10 subst/site), consistent with multiple founders. By incorporating sequence data collected from the source partner, we were able to characterize all thirty transmission pairs. Overall, sixteen transmission events (53.3 percent) involved multiple founders. Results obtained by combining sequence data from recipient and source were congruent for nineteen of the twenty-six (73 percent) cases where conclusions were made using only recipient sequence data. The multiplicity of founders was associated with significantly higher HIV RNA levels (P = 0.04). To further evaluate the transmission bottleneck, we focused on single founder transmissions (fourteen of the thirty), and identified four recipients (28.6 percent) that had founder variants that were inferred to arise from minority viral populations in the source. These source clades ranged from 1.0 to 5.4 percent of the sampled population. Incorporating sequence data from the source increased of the ability to determine the multiplicity of founder variants, reduced misclassification, and allowed us to infer the transmission of minority variants.

Project description:BackgroundIn Sudan, where studies on HIV dynamics are few, model projections provide an additional source of information for policy-makers to identify data collection priorities and develop prevention programs. In this study, we aimed to estimate the distribution of new HIV infections by mode of exposure and to identify populations who are disproportionately contributing to the total number of new infections in Sudan.MethodsWe applied the modes of transmission (MoT) mathematical model in Sudan to estimate the distribution of new HIV infections among the 15-49 age group for 2014, based on the main routes of exposure to HIV. Data for the MoT model were collected through a systematic review of peer-reviewed articles, grey literature, interviews with key participants and focus groups. We used the MoT uncertainty module to represent uncertainty in model projections and created one general model for the whole nation and 5 sub-models for each region (Northern, Central, Eastern, Kurdufan, and Khartoum regions). We also examined how different service coverages could change HIV incidence rates and distributions in Sudan.ResultsThe model estimated that about 6000 new HIV infections occurred in Sudan in 2014 (95% CI: 4651-7432). Men who had sex with men (MSM) (30.52%), female sex workers (FSW) (16.37%), and FSW's clients accounted (19.43%) for most of the new HIV cases. FSW accounted for the highest incidence rate in the Central, Kurdufan, and Khartoum regions; and FSW's clients had the highest incidence rate in the Eastern and Northern regions. The annual incidence rate of HIV in the total adult population was estimated at 330 per 1 000 000 populations. The incidence rate was at its highest in the Eastern region (980 annual infections per 1 000 000 populations).ConclusionAlthough the national HIV incidence rate estimate was relatively low compared to that observed in some sub-Saharan African countries with generalized epidemics, a more severe epidemic existed within certain regions and key populations. HIV burden was mostly concentrated among MSM, FSW, and FSW's clients both nationally and regionally. Thus, the authorities should pay more attention to key populations and Eastern and Northern regions when developing prevention programs. The findings of this study can improve HIV prevention programs in Sudan.

Dataset Information

Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

Publications

Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets