HIV-1 Vpr induces DNA double-strand breaks.
Recent observations imply that HIV-1 infection induces chromosomal DNA damage responses. However, the precise molecular mechanism and biological relevance are not fully understood. Here, we report that HIV-1 infection causes double-strand breaks in chromosomal DNA. We further found that Vpr, an accessory gene product of HIV-1, is a major factor responsible for HIV-1-induced double-strand breaks. The purified Vpr protein promotes double-strand breaks when incubated with isolated nuclei, although it does not exhibit endonuclease activity in vitro. A carboxyl-terminally truncated Vpr mutant that is defective in DNA-binding activity is less capable of Vpr-dependent double-strand break formation in isolated nuclei. The data suggest that double-strand breaks induced by Vpr depend on its DNA-binding activity and that Vpr may recruit unknown nuclear factor(s) with positive endonuclease activity to chromosomal DNA. This is the first direct evidence that Vpr induces double-strand breaks in HIV-1-infected cells. We discuss the possible roles of Vpr-induced DNA damage in HIV-1 infection and the involvement of Vpr in further acquired immunodeficiency syndrome-related tumor development.
Tachiwana
Hiroaki
H
Graduate School of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, 169-8555 Tokyo, Japan.
Shimura
Mari
M
Nakai-Murakami
Chikako
C
Tokunaga
Kenzo
K
Takizawa
Yoshimasa
Y
Sata
Tetsutaro
T
Kurumizaka
Hitoshi
H
Ishizaka
Yukihito
Y
D018929:Cell Culture Techniques; D002875:Chromosomes; D004249:DNA Damage; D016336:Gene Products, vpr / Q000502:physiology*; D015658:HIV Infections / Q000235:genetics* / Q000503:physiopathology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D016867:Immunocompromised Host; D054325:vpr Gene Products, Human Immunodeficiency Virus
D016336:Gene Products, vpr; D054325:vpr Gene Products, Human Immunodeficiency Virus