Human immunodeficiency virus type 1 reverse transcriptase: enhancement of activity by interaction with cellular topoisomerase I.
A number of studies have suggested that topoisomerase I (topo I) activity may be important in human immunodeficiency virus type 1 (HIV-1) replication. Specifically it has been reported that purified virus particles have topo I activity and that inhibitors of this enzyme can inhibit virus replication in vitro. We have investigated a possible association of HIV-1 gag proteins with topo I activity. We found that whereas the gag-encoded proteins by themselves do not have activity, the nucleocapsid protein p15 can interact with and enhance the activity of cellular topo I. Furthermore it could be demonstrated that topo I markedly enhanced HIV-1 reverse transcriptase activity in vitro and that this could be inhibited by the topo I-specific inhibitor camptothecin. The findings suggest that cellular topo I plays an important role in the reverse transcription of HIV-1 RNA and that the recruitment of this enzyme may be an important step in virus replication.
Takahashi
H
H
Department of Pathology, National Institute of Health, Tokyo, Japan.
Matsuda
M
M
Kojima
A
A
Sata
T
T
Andoh
T
T
Kurata
T
T
Nagashima
K
K
Hall
W W
WW
D001483:Base Sequence; D017931:DNA Primers; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D015683:Gene Products, gag / Q000502:physiology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000235:genetics; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D014158:Transcription, Genetic; D014779:Virus Replication
D017931:DNA Primers; D015683:Gene Products, gag; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D004264:DNA Topoisomerases, Type I