Selection, recombination, and G----A hypermutation of human immunodeficiency virus type 1 genomes.
Human immunodeficiency virus type 1 (HIV-1) isolates are genetically so heterogeneous that they must be described in terms of populations of related but distinct genomes called quasispecies. A recent study of the influence of ex vivo culturing on HIV-1 quasispecies demonstrated that usually low-abundance genomes outgrew the more prominent forms. Here it is shown that multiple passages of an HIV-1 isolate on peripheral blood mononuclear cells resulted in the outgrowth of very minor forms. A single passage of equal proportions of supernatants to either of the established lymphocyte and monocyte cell lines Molt-3 and U937-2, respectively, resulted in the isolation of different sets of minor forms. Recombination between component sequences was observed. Extensive and monotonous base substitutions of G----A (G----A hypermutation) were evident in many sequences. A strong preference for the transition within the GpA dinucleotide was observed. Dislocation mutagenesis, in this case, a -1 slippage or dislocation of the primer with respect to the template, during DNA synthesis by the HIV-1 reverse transcriptase would explain this bias. When the consequences of polymerase errors, recombination, hypermutation, and instability are added to the genetic description of HIV-1, the real complexity of this virus starts to become apparent.
Vartanian
J P
JP
Laboratoire de Rétrovirologie Moléculaire, Institut Pasteur, Paris, France.
Meyerhans
A
A
Asjö
B
B
Wain-Hobson
S
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000737:chemistry; D015686:Gene Products, env / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D014779:Virus Replication
D004279:DNA, Viral; D015686:Gene Products, env