The central DNA flap of the human immunodeficiency virus type 1 is important for viral replication.
Reverse transcription of the human immunodeficiency virus type 1 is characterized by the formation of a DNA flap at the center of the viral cDNA in between the central polypurine tract (cPPT) and the central termination sequence (CTS). The importance of the DNA flap for HIV-1 replication has been questioned, whereas its importance for lentiviral vector performance is well accepted. To investigate this controversy, we re-evaluated the importance of the DNA flap for HIV-1 replication. A flap negative HIV-1 virus showed a 10- to 100-fold replication defect in comparison with a WT strain. Further characterization of the DNA flap in the context of lentiviral vectors showed that mutations in the DNA-flap sequence did not affect the transduction efficiency. Finally, introduction of a second cPPT/CTS sequence resulted in the presence of two DNA flaps but no higher transduction efficiency.
De Rijck
Jan
J
Laboratory for Molecular Virology and Gene Therapy, KULeuven and IRC KULAK, Leuven, Belgium.
Debyser
Zeger
Z
D001483:Base Sequence; D002460:Cell Line; D004261:DNA Replication / Q000235:genetics*; D004279:DNA, Viral / Q000096:biosynthesis* / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D016086:Lentivirus / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D016415:Sequence Alignment
D004279:DNA, Viral