The nature of human immunodeficiency virus type 1 strand transfers.
The diploid nature of human immunodeficiency virus type 1 (HIV-1) suggests that recombination serves a central function in virus replication and evolution. A system was developed to examine HIV-1 strand transfers, including the obligatory DNA primer strand transfers as well as recombinational crossovers during reverse transcription. Sequence heterogeneity between different strains of HIV-1 was exploited for examining primer transfer events. Both intra- and intermolecular primer transfers were observed at similar frequencies during minus-strand DNA synthesis, whereas primer transfers during plus-strand DNA synthesis were primarily intramolecular. Sequence analysis of long terminal repeats from progeny proviruses also revealed a high rate of homologous recombination during minus-strand synthesis, corresponding to an overall rate of approximately three crossovers per HIV-1 genome per cycle of replication. These results imply that both viral genomic RNAs serve as templates during HIV-1 reverse transcription and that primer strand transfers and recombination may contribute substantially to the rapid genetic variation of HIV-1.
Department of Molecular Genetics and Microbiology, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
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D001483:Base Sequence; D003434:Crossing Over, Genetic; D017931:DNA Primers; D004171:Diploidy; D005822:Genetic Vectors; D016679:Genome, Viral; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D014779:Virus Replication / Q000235:genetics
D017931:DNA Primers; D012367:RNA, Viral