THE NATURE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 STRAND TRANSFERS

The diploid nature of human immunodeficiency virus type 1 (HIV-1) sugg ests that recombination serves a central function in virus replication and evolution. A system was developed to examine HIV-1 strand transfe rs, including the obligatory DNA primer strand transfers as well as re combinational crossovers during reverse transcription. Sequence hetero geneity between different strains of HIV-1 was exploited for examining primer transfer events. Both intra- and intermolecular primer transfe rs were observed at similar frequencies during minus-strand DNA synthe sis, whereas primer transfers during plus-strand DNA synthesis were pr imarily intramolecular. Sequence analysis of long terminal repeats fro m progeny proviruses also revealed a high rate of homologous recombina tion during minus-strand synthesis, corresponding to an overall rate o f approximately three crossovers per HIV-1 genome per cycle of replica tion. These results imply that both viral genomic RNAs serve as templa tes during HIV-1 reverse transcription and that primer strand transfer s and recombination may contribute substantially to the rapid genetic variation of HIV-1.