Speaker
Description
HIV- is a highly adaptive virus that due to its high mutation rate and yield adapts to diverse evolutionary challenges, thereby complicating containment and treatment of the virus. To further understand HIV-1’s genomic evolution, we have utilized the genomic and phenotypic data obtained from our longest HIV-1 evolution experiment, corresponding to 5 years of virus passaging, in two replicates of MT-2 and MT-4 cell cultures. We have obtained insights into the repeatability, and hence predictability, of evolution in this fast-evolving virus, while also elucidating the roles of environmental factors and population size. In all populations, we observe continuation of linear accumulation of fixed variants (at the rate of 0.12 and 0.06 substitution per generation in MT-2 and MT-4, respectively). We found ~20% of all observed variants fixed in the populations to be shared among at least 2 independent evolutionary lines. Repeated variants exhibit distinctive fixation dynamics, characterized by early emergence and faster fixation kinetics. The scope of parallelism in genomic evolution of HIV-1 is not limited to the recurrence of specific variants, but extends to similar evolutionary forces acting upon different genomic regions. We see similar levels of genetic variation maintained within each gene which is predictive of the parallelism. Moreover, we delineated how the virus streamlines its genome and reproducibly disposes of elements that are likely not advantageous to its reproductive success in our experimental setup, such as the nef gene. Additionally, titration assay and estimation of effective population sizes indicate that population sizes are 4-6 fold higher in MT-4 lines. In concordance with larger population sizes, in MT-4 evolution is considerably more predictable which can be attributed to stronger selection and weakened drift. In summary, we show that evolution can be predicted to varying degrees for clinically relevant viruses with unmet medical challenges.
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