Different evolutionary patterns are found within human immunodeficiency virus type 1-infected patients

Abstract

In order to study the evolution in vivo of human immunodeficiency virus type 1 (HIV-1) in patients with normal clinical evolution, six individuals were selected from a group of 46 patients followed for 1 to 4 years. Patients were selected not by clinical progression characteristics but on the basis of virus genetic variability, as analysed by heteroduplex mobility assay and RNase A mismatch cleavage method. Two patients displayed a homogeneous virus population, two showed very heterogeneous quasispecies and two presented two distinct variants within the virus population. Virus quasispecies were studied by nucleotide sequencing of the C2-fusion domain of the env gene. Virus evolution was approached by analysing the distribution of genetic distances, calculation of divergence and heterogeneity as well as the K a/K s ratio and by the construction of the phylogenetic trees. Three patients displayed the same tree topology, characterized by the presence of independent clades supported by high bootstrap values, whereas this pattern was not present in the other three patients. In the three patients displaying independent clades, a recombination analysis was carried out between distinct subpopulations and recombinant variants were identified. In one patient of this group, different selective pressures were detected in distinct virus clades, measured by their corresponding K a/K s ratios, revealing that different evolutionary forces are occurring at the same time within the same patient. These results show that multiple evolutionary patterns can be found in typical HIV-1-infected patients.