期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 102, 期 25, 页码 9002-9007出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0502522102
关键词
subtype; RNA dimerization
Genetic recombination increases diversity in HIV-1 populations, thereby allowing variants to escape from host immunity or antiviral therapies. In addition to the currently described nine subtypes of HIV-1, many of the circulating strains are intersubtype recombinants. In this study, we determined the recombination rate between two HIV-1 subtype C viruses and between a subtype B virus and a subtype C virus during a single round of virus replication. Although HIV-1 subtype C recombines at a high rate, similar to that of HIV-1 subtype B, the recombination rate between a subtype B virus and a subtype C virus is much lower than the intrasubtype recombination rate. A 3-nt sequence difference in the dimerization initiation signal (DIS) region between HIV-1 subtypes B and C accounts for most of the reduction of intersubtype recombination. By matching the DIS sequences, the B/C intersubtype recombination rate was elevated 4-fold; by introducing mismatches in the 3-nt sequences, the B/B intrasubtype recombination rate was reduced 4-fold. Further analyses showed that the intermolecular template-switching frequency was unaffected by the sequence identity of the DIS region. These results support the hypothesis that mismatched sequences in the DIS region alter the formation of heterozygous virions, thereby lowering the observable recombination rate. Here, we present the discovery of a major restriction in HIV-1 intersubtype recombination. These results have important implications for virus evolution, the mechanism of HIV-1 RNA packaging, high negative interference in recombination, and the generation of circulating intersubtype recombinants within the infected population.
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