Publication: Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus
Open/View Files
Date
2016
Published Version
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
The Harvard community has made this article openly available. Please share how this access benefits you.
Citation
Tully, D. C., C. B. Ogilvie, R. E. Batorsky, D. J. Bean, K. A. Power, M. Ghebremichael, H. E. Bedard, et al. 2016. “Differences in the Selection Bottleneck between Modes of Sexual Transmission Influence the Genetic Composition of the HIV-1 Founder Virus.” PLoS Pathogens 12 (5): e1005619. doi:10.1371/journal.ppat.1005619. http://dx.doi.org/10.1371/journal.ppat.1005619.
Research Data
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.
Description
Other Available Sources
Keywords
Biology and Life Sciences, Microbiology, Medical Microbiology, Microbial Pathogens, Viral Pathogens, Immunodeficiency Viruses, HIV, HIV-1, Medicine and Health Sciences, Pathology and Laboratory Medicine, Pathogens, Organisms, Viruses, Biology and life sciences, RNA viruses, Retroviruses, Lentivirus, Virology, Viral Transmission and Infection, Evolutionary Biology, Evolutionary Processes, Natural Selection, Population Genetics, Genetics, Population Biology, Evolutionary Systematics, Phylogenetics, Taxonomy, Computer and Information Sciences, Data Management, Molecular biology, Molecular biology techniques, Sequencing techniques, Sequence analysis, DNA sequence analysis, People and Places, Population Groupings, Sexual Preferences, Men WHO Have Sex with Men, Molecular Biology, Molecular Biology Techniques, Sequencing Techniques, Genome Sequencing, Genomics, Microbial Genomics, Viral Genomics
Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material (LAA), as set forth at Terms of Service