Abstract
The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Yet, little is known about the distribution of selection differentials between individual viruses and the impact of single polymorphisms on viral fitness. Here, we estimate the rate of recombination and the distribution of selection coefficients from time series sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be ρ = 1.4±0.6×10−5 recombinations per site and generation. Furthermore, we provide evidence that the selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible as soon as data with higher time resolution and greater sample sizes are available.
Highlights
The human immunodeficiency virus (HIV-1) ranks among the most rapidly evolving entities known [1], enabling the virus to continually escape the immune system
The genotypic diversity is subject to positive selection for novel variants that are not recognized by the host immune system or that reduce the sensitivity to anti-retroviral drugs [5,6,7], as well as to purifying selection by functional constraints [8]
We study the strength of selection exerted on the virus by the immune system
Summary
The human immunodeficiency virus (HIV-1) ranks among the most rapidly evolving entities known [1], enabling the virus to continually escape the immune system. The number of virions produced and removed is estimated to be around 1010 per day with a generation time slightly less than two days [2] Due to this rapid turnover and the high mutation rate of 2:5|10{5 per site and generation, the sequence diversity of HIV within a single patient can rise to &5% ( env gene) within a few years and the divergence from the founder strain increases by &1% per year [3], this rate is not constant [4]. In addition to high substitution rates and strong selection, genomes of different HIV particles within the same host frequently exchange genetic information. This form of viral recombination works as follows: Whenever a cell is coinfected by two or more viruses, the daughter virions can contain two RNA strands from different viruses[9,10]. In cases of super-infection with several HIV-1 subtypes, recombination can give rise to novel forms that become part of the global epidemic [14]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call