Human topoisomerase I promotes HIV-1 proviral DNA synthesis: implications for the species specificity and cellular tropism of HIV-1 infection.
Although HIV type 1 (HIV-1) cannot efficiently replicate in simian cells, the mechanism(s) involved in the restriction of virus tropism remain unclear. To investigate this, we have focused on the identification of human cellular factors that can influence the infectivity of HIV-1 derived from African green monkey producer cells. Whereas the infectivity of HIV-1 derived from such cells was only 10-15% of that of human cell-derived virus, expression of human topoisomerase I in the African green monkey cells resulted in a 5-fold increase of the infectivity of progeny HIV-1 virions. Replacement of glutamate-236 and asparagine-237 of human topoisomerase I with the corresponding residues (aspartate and serine, respectively) of the African green monkey enzyme abolished this enhancement of HIV-1 infectivity. This positive effect of human topoisomerase I expression in the African green monkey producer cells seemed to result from the promotion of HIV-1 cDNA synthesis. Thus, human topoisomerase I plays an important role in HIV-1 replication and infectivity, and differences in the species specificity of HIV-1 infection can at least in part be attributed to differences in topoisomerase I activities.
Shoya
Yuko
Y
Department of Pathology, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640, Japan.
Tokunaga
Kenzo
K
Sawa
Hirofumi
H
Maeda
Masae
M
Ueno
Tomonori
T
Yoshikawa
Tomoki
T
Hasegawa
Hideki
H
Sata
Tetsutaro
T
Kurata
Takeshi
T
Hall
William W
WW
Cullen
Bryan R
BR
Takahashi
Hidehiro
H
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells / Q000821:virology; D002460:Cell Line / Q000821:virology; D002522:Chlorocebus aethiops; D003062:Codon; D004261:DNA Replication; D004264:DNA Topoisomerases, Type I / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018076:DNA, Complementary / Q000235:genetics; D004279:DNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D017930:Genes, Reporter; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells / Q000821:virology; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000196:embryology; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D008969:Molecular Sequence Data; D011533:Proviruses / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014162:Transfection; D014709:Vero Cells / Q000821:virology; D014776:Virus Cultivation; D014779:Virus Replication
D003062:Codon; D018076:DNA, Complementary; D004279:DNA, Viral; D011993:Recombinant Fusion Proteins; D008156:Luciferases; D004264:DNA Topoisomerases, Type I