Viral load minimally affects the intra-host recombination rate of HIV
Authors: Elena Romero; Alison Feder
Affiliation: University of Washington, Seattle, WA
Keywords: Other (Viral Evolution)
Intra-host recombination generates new mutational combinations which enable immune escape and multidrug resistance in HIV. Because HIV recombines via coinfection, denser HIV populations may have higher rates of coinfection and therefore recombination, but the potential impact of viral density on recombination has not been previously quantified. Using viral load as a proxy for viral density, we analyze longitudinal, high-throughput viral sequencing data from individuals with HIV viral loads varying by orders of magnitude to quantify different recombination rates as a function of viral load. We use two methods to quantify recombination in time series: one based on the autocorrelation of linkage over time and one based on the differential discovery rate of haplotypes likely to be created via recombination as a function of distance. We validate these methods on extensive simulated data and find that the recombination rate estimation is distorted significantly by natural selection and overbinning genetic variation. We then identify a set of best practices for estimating recombination in genetic time series similar to those sampled in intra-host viral evolution. Using these best practices, we estimate effective recombination rates in viral populations with low (<10^4 viral copies/mL) and high (>10^4 viral copies/mL) and find, surprisingly, that viral load does not significantly affect recombination rate. The independence of viral load and recombination rate suggests that recombination is an important driver of viral evolution even in viremic controllers (individuals with setpoint viral load <=2*10^3 copies/mL), and that important viral population parameters can not be well-approximated by convenience sampling in the blood. These results inform our understanding of recombination in viruses more broadly, and may help us understand the structure of where viruses replicate in the body.