Abstract
Human Immunodeficiency Virus type 1 (HIV-1) because of high mutation rates, large population sizes, and rapid replication, exhibits complex evolutionary strategies. For the analysis of evolutionary processes, the graphical representation of fitness landscapes provides a significant advantage. The experimental determination of viral fitness remains, in general, difficult and consequently most published fitness landscapes have been artificial, theoretical or estimated. Self-Organizing Maps (SOM) are a class of Artificial Neural Network (ANN) for the generation of topological ordered maps. Here, three-dimensional (3D) data driven fitness landscapes, derived from a collection of sequences from HIV-1 viruses after “in vitro” passages and labelled with the corresponding experimental fitness values, were created by SOM. These maps were used for the visualization and study of the evolutionary process of HIV-1 “in vitro” fitness recovery, by directly relating fitness values with viral sequences. In addition to the representation of the sequence space search carried out by the viruses, these landscapes could also be applied for the analysis of related variants like members of viral quasiespecies. SOM maps permit the visualization of the complex evolutionary pathways in HIV-1 fitness recovery. SOM fitness landscapes have an enormous potential for the study of evolution in related viruses of “in vitro” works or from “in vivo” clinical studies with human, animal or plant viral infections.
Highlights
Human Immunodeficiency Virus type 1 (HIV-1) is characterized by high mutation rates, large population sizes, and rapid replication rates
This report on the ‘‘in vitro’’ viral evolution in HIV-1 depicts the first fitness landscapes constructed with realistic viral data
This Self-Organizing Maps (SOM) map permitted the aproximation to the fitness value, based on the similarity of the sequence, of members of viral quasispecies and the visualization of the evolutionary pathways of the different HIV-1 variants during the serial passages
Summary
Human Immunodeficiency Virus type 1 (HIV-1) is characterized by high mutation rates, large population sizes, and rapid replication rates. HIV-1 ‘‘in vitro’’ studies after serial culture passages with alterations in the population size have been used for the simulation and study of viral evolution (Figure 1 and 2) [3,4,5,6,7]. For the investigation on the evolution of organisms, Sewall Wright [9] depicted the change in allele frequency for the production of adaptative landscapes. These landscapes were primarily used for the illustration of evolutionary pathways. Afterwards, they were extended with the concept of sequence space [10] and for the generation of fitness landscapes [11,12]. Most fitness landscapes have been artificial, theoretical or estimated [13] and realistic fitness landscapes are lacking [28]
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