Human immunodeficiency virus bearing a disrupted central DNA flap is pathogenic in vivo.
The central DNA flap is an important component of lentiviral vectors, but its significance in the context of wild-type human immunodeficiency virus (HIV) is currently unclear. To address this issue, we have compared the in vitro infection kinetics of NL4-3 with those of a flap-deficient mutant and evaluated the in vivo growth characteristics of these viruses by using the SCID-hu mouse model of HIV infection. Flap-deficient virus was only modestly attenuated in vitro, as assessed by single-round and spreading infection assays, and exhibited levels of replication and pathogenesis close to those of the wild-type in vivo. Hence, an intact central flap is not essential for HIV replication.
Marsden
Matthew D
MD
Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Zack
Jerome A
JA
D000818:Animals; D004279:DNA, Viral / Q000737:chemistry* / Q000235:genetics*; D006678:HIV / Q000737:chemistry* / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D009690:Nucleic Acid Conformation; D017384:Sequence Deletion; D014779:Virus Replication / Q000502:physiology*
D004279:DNA, Viral